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Extracellular vesicles (EVs) are small particles released by many cell types in different tissues, including the liver, and transfer specific cargo molecules from originating cells to receptor cells. This process generally culminates in activation of distant cells and inflammation and progression of certain diseases. The global chronic liver disease (CLD) epidemic is estimated at 1.5 billion patients worldwide. Cirrhosis and liver cancer are the most common risk factors for CLD. However, hepatitis C and B virus infection and obesity are also highly associated with CLD. Nonetheless, the etiology of many CLD pathophysiological, cellular, and molecular events are unclear. Changes in hepatic lipid metabolism can lead to lipotoxicity events that induce EV release. Here, we aimed to present an overview of EV features, from definition to types and biogenesis, with particular focus on the molecules related to steatosis-related liver disease, diagnosis, and therapy.

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Abstract Bioactive cements based on tricalcium silicate have been introducedto the market for use in dentistry, with a variety of clinical applications. These cements are in contact with vital tissues such as dental pulp or periodontium in cases of unintentional extrusion; thus, it is important to know the genotoxicity and cytoxicity of these materials. The objective of this study was to evaluate the cytotoxicity and genotoxicity of bioactive sealers, Bio-C® Sealer and MTA Repair HP®, in human fibroblasts. Discs of bioactive sealers Bio-C® Sealer, and MTA Repair HP®, were prepared and set for 24h under sterile conditions. The discs were placed in culture medium at 2.5mg/mL inside a SRT6D roller mixer (Stuart, UK) at 60rpm for 24h. The eluates obtained were incubated for 24h with previously activated and cultured ATCC cell line fibroblasts at 80% confluence. The cytotoxicity was evaluated by Alamar Blue® and LIVE/ DEAD assays, as well as the analysis of the Tunel and Mitotracker assays to evaluate genotoxicity using the confocal laser-scanning microscope. In the Alamar Blue® assay, the Bio-C® Sealer presented a cell proliferation of 87%, while the MTA Repair HP® Sealer was 72%. A statistically significant difference was found between the MTA Repair HP® Sealant and the negative control (p=<0.001). Regarding the genotoxicity tests, in the Tunel assay, both materials stain the nucleus of the fibroblast cells exposed to the eluates, while in the Mitotracker assay, the MTA Repair HP® Sealer showed greater mitochondrial function than the Bio-C® Sealer. Calcium silicate-based sealers, Bio-C® Sealer and MTA Repair HP®, are not cytotoxic and have low genotoxicity.

Resumen Los cementos bioactivos a base de silicato tricálcico se introdujeron en el mercado para uso en odontología, con una variedad de aplicaciones clínicas. Estos cementos pueden estar en contacto con tejidos como la pulpa dental o el periodonto, en caso de extrusión no intencionada. Por lo tanto, es importante conocer la genotoxicidad y la citoxicidad de estos materiales. El objetivo de este estudio fue evaluar la citotoxicidad y genotoxicidad de los selladores bioactivos Bio-C® Sealer y MTA Repair HP® en fibroblastos humanos. Se prepararon discos de selladores bioactivos Bio-C® Sealer y MTA Repair HP® y se colocaron durante 24h en condiciones de esterilidad. Los discos se colocaron en medio de cultivo a 2,5mg/mL dentro de un mezclador de rodillos SRT6D (Stuart, Reino Unido) a 60rpm durante 24h. Los eluidos obtenidos se incubaron durante 24h con fibroblastos de la línea celular ATCC previamente activados y cultivados al 80% de confluencia. La citotoxicidad se evaluó mediante ensayos Alamar Blue® y LIVE/DEAD; así como el análisis de los ensayos Tunnel y Mitotracker para evaluar la genotoxicidad, utilizando el microscopio confocal láser de barrido. En el ensayo Alamar Blue®, el Sellador Bio-C® presentó una proliferación celular del 87%, mientras que el sellador MTA Repair HP® fue del 72%. Se encontró una diferencia estadísticamente significativa entre el sellador MTA Repair HP® con respecto al control negativo (p=<0.001). En cuanto a las pruebas de genotoxicidad, en el ensayo Tunel, ambos materiales tiñen el núcleo de las células fibroblásticas expuestas a los eluidos, mientras que el ensayo Mitotracker, el sellador MTA Repair HP®, mostró una mayor función mitocondrial que el Bio-C® Sealer. Los selladores a base de silicato de calcio, Bio-C® Sealer y MTA Repair HP® no son citotóxicos y tienen una baja genotoxicidad.

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Background: Intracanal medication is considered an alternative after instrumentation in the case of pulp necrosis. However, the elimination of this medication plays an important role in the obturation process, which is why various chelating solutions have currently been studied for this purpose. Therefore, this study aimed to analyze the irrigant based on alendronic acid (AA), which contains in its chemical structure functional groups capable of forming complexes with Ca2+ ions. Material and Methods: 90 single-rooted teeth were crowned and standardized to a length of 13 mm. They were instrumented with a progressive K file (Dentsply Maillefer) from #15 to #30. Ca(OH)2 was placed as intracanal medication for 7 days. The roots were randomly divided into the following 4 experimental groups (n=13) according to the irrigant used: 2.25% NaClO, calcium suspension, 0.22% AA, and 10% citric acid; as well as negative (n=5; saline solution) and positive controls (n=5, 17% EDTA). The roots were divided longitudinally and the % of permeable dentinal tubules (% PDT) was determined by thirds (cervical, middle and apical), by analyzing the micrographs obtained by scanning electron microscope (SEM) and the imageJ program. The quantification of the remaining Ca2+ was determined using the Arsenazo III technique. Results: The Kruskal Wallis test was used for the % of permeable dentinal tubules where a significant difference was determined for the different thirds (p<0.005). In the apical third, citric acid and AA irrigants presented a median of 17.71 and 17.51 % PDT respectively. In relation to the quantification of the remaining total calcium, the lowest value was found with AA with a concentration of 4.83 mmol/L. Conclusions: The 0.22% AA solution has the same capacity to remove Ca(OH)2 from the root canal walls as 17% EDTA and 10% citric acid. Key words:Alendronic acid, calcium hydroxide, citric acid, EDTA, irrigant solution,root canal.

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Lignocellulosic biomass is widely available in the world. However, a consensus has yet to be established to evaluate the biomass valorization alternatives. The chemical composition is the primary technical limitation in selecting a transformation route to obtain value-added products. In this paper, the bagasse from non-centrifuged sugar (NCS) production and Pinus patula (PP) wood chips were analyzed in terms of complete chemical composition to establish their potential for selecting the transformation routes. A strategy to select the best route based on the chemical composition was applied and a feedstock criteria model was proposed. Schemes were obtained and compared using a bioprocess selection strategy proposed in previous works. As a result, the preliminary biorefinery schemes were finally defined. The assessment of schemes derived from the outlined strategy included technical, economic, environmental, and social analyses. The environmental evaluation was complemented with a geolocation assessment, revealing a 0.75-ton CO2-eq/yr contribution to the carbon footprint for local distribution. The sustainability index for the PP biorefinery and the bagasse from NCS production was analyzed, resulting in indices of 44.8 and 60.9, respectively. These values were primarily derived from the economic and environmental analyses of both processes.

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Inland waters are crucial in the carbon cycle, contributing significantly to the global CO2 fluxes. Carbonate lakes may act as both sources and sinks of CO2 depending on the interactions between the amount of dissolved inorganic carbon (DIC) inputs, lake metabolisms, and geochemical processes. It is often difficult to distinguish the dominant mechanisms driving CO2 dynamics and their effects on CO2 emissions. This study was undertaken in three groundwater-fed carbonate-rich lakes in central Spain (Ruidera Lakes), severely polluted with nitrates from agricultural overfertilization. Diel and seasonal (summer and winter) changes in CO2 concentration (CCO2) DIC, and CO2 emissions-(FCO2)-, as well as physical and chemical variables, including primary production and phytoplanktonic chlorophyll-a were measured. In addition, δ13C-DIC, δ13C-CO2 in lake waters, and δ13C of the sedimentary organic matter were measured seasonally to identify the primary CO2 sources and processes. While the lakes were consistently CCO2 supersaturated and FCO2 was released to the atmosphere during both seasons, the highest CCO2 and DIC were in summer (0.36-2.26 µmol L-1). Our results support a strong phosphorus limitation for primary production in these lakes, which impinges on CO2 dynamics. External DIC inputs to the lake waters primarily drive the CCO2 and, therefore, the FCO2. The δ13C-DIC signatures below -12‰  confirmed the primary geogenic influence on DIC. As also suggested by the high values on the calcite saturation index, the Miller-Tans plot revealed that the CO2 source in the lakes was close to the signature provided by the fractionation of δ13C-CO2 from calcite precipitation. Therefore, the main contribution behind the CCO2 values found in these karst lakes should be attributed to the calcite precipitation process, which is temperature-dependent according to the seasonal change observed in δ13C-DIC values. Finally, co-precipitation of phosphate with calcite could partly explain the observed low phytoplankton production in these lakes and the impact on the contribution to increasing greenhouse gas emissions. However, as eutrophication increases and the soluble reactive phosphorus (SRP) content increases, the co-precipitation of phosphate is expected to be progressively inhibited. These thresholds must be assessed to understand how the CO32- ions drive lake co-precipitation dynamics. Carbonate regions extend over 15% of the Earth's surface but seem essential in the CO2 dynamics at a global scale.

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(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

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The seed germination, as well as root and shoot growth effect of HKUST-1 MOF, and its derived linear polymer ([Cu2(OH)(BTC)(H2O)]n·2nH2O) were herein examined. These effects were studied for seven higher plant species: sweet corn (Zea mays L.), black bean (Phaseolus vulgaris L.), tomato (Solanum lycopersicum L.), lettuce (Lactuca sativa L.), celosia (Celosia argentea L.), Aztec marigold (Tagetes erecta L.), and gypsophila (Gypsophila paniculata L.). The studied concentrations of MOFs were 10, 100, 500, or 1000 mg/L, enhancing the percentage of germination and growth of plants in most species. In general, the growth of the root is lower compared to the controls due to the capacity of the MOF to adsorb water and provide micronutrients such as C, O, and Cu, acting as a reserve for the plant. Shoot system growths are more pronounced with HKUST-1 compared with control, and linear polymer, due to the 3D structure adsorbs major water contents. It was found that all studied species are tolerant not only to Cu released from the material, but more evident to Cu structured in MOFs, and this occurs at high concentrations compared to many other systems. Finally, copper fixation was not present, studied by EDX mapping, banning the possibility of metallic phytotoxicity to the tested cultivars.

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Adequately reporting of preeclampsia is a challenge. The aim of this study was to compare the diagnosis of preeclampsia based on clinical and laboratory findings and ICD-10 codes (International Classification of Diseases) at admission and discharge in a referral center, over a one-year period. Among 2,839 women admitted for childbirth, 208 presented confirmed preeclampsia, based on chart audits. Among these, 77.4% at admission presented ICD-10 codes assigned as hypertension, and 47.1% at discharge. In 14.4% of confirmed preeclampsia, ICD-10 codes for hypertension were not used. Adequate reporting of preeclampsia is key for clinical surveillance, counselling and guiding public health interventions.

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The ß2 integrin CD11b/CD18, also known as complement receptor 3 (CR3), and the moonlighting protein aminopeptidase N (CD13), are two myeloid immune receptors with overlapping activities: adhesion, migration, phagocytosis of opsonized particles, and respiratory burst induction. Given their common functions, shared physical location, and the fact that some receptors can activate a selection of integrins, we hypothesized that CD13 could induce CR3 activation through an inside-out signaling mechanism and possibly have an influence on its membrane expression. We revealed that crosslinking CD13 on the surface of human macrophages not only activates CR3 but also influences its membrane expression. Both phenomena are affected by inhibitors of Src, PLCγ, Syk, and actin polymerization. Additionally, after only 10 min at 37 °C, cells with crosslinked CD13 start secreting pro-inflammatory cytokines like interferons type 1 and 2, IL-12p70, and IL-17a. We integrated our data with a bioinformatic analysis to confirm the connection between these receptors and to suggest the signaling cascade linking them. Our findings expand the list of features of CD13 by adding the activation of a different receptor via inside-out signaling. This opens the possibility of studying the joint contribution of CD13 and CR3 in contexts where either receptor has a recognized role, such as the progression of some leukemias.

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Background: Gutta-percha (Gp) is an inert thermoplastic polymer used as a filling to replace the dental pulp space, which has been reformulated to improve its three-dimensional sealing properties. Therefore, this study aimed to analyze the physical, chemical and thermal properties of two types of gutta-percha filling. As well as measuring the temperature distribution along the cone at the time of cutting through an in-situ test. Material and Methods: Two commercially available brands of gutta-percha point were investigated: Conform Fit TM Gutta-Percha for ProTaper Gold® (PTG) (Dentsply Sirona), and Hygenic Gutta-Percha (Coltene whaledent). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were selected for the thermal characterization of materials, and Fourier Transform Infrared Spectroscopy (FT-IR) for the chemical analysis of Gp cones. Regarding temperature distribution, it was evaluated using a thermographic camera (FLIR ONE® PRO by MicroUSB P/N 435-0011-01) at 0 to 20 s after the cutting process (n=11/group). Results: Both materials have three fusion endotherms associated with the three crystalline phases of Gp, with similar temperatures but enthalpies that differ by 60%, the fusion enthalpy being higher for Conform Fit. In the chemical characterization, elements such as Zn, C, O, Ba, S and Si were found in both materials but in different proportions. Regarding the content of fillers, the Conform Fit presented around 30% of Gp polymer and 25% for the Hygenic. The morphological characterization shows a microtexturized coating in the form of bars on a micrometric scale for the Conform Fit, which could favor a better three-dimensional seal. In addition to that, in heat transfer studies they showed greater temperature control. Conclusions: The characterization of the materials allowed us to see the variation in terms of their composition and configuration to the Gp cones of two commercial brands. These variations directly modify the thermal behavior of the material. Key words:Gutta-percha, Conform Fit, Infrared thermography, Differential Scanning Calorimetry, Infrared Spectroscopy.

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Introduction: Although studies with informal workers have been conducted in Latin America and the Caribbean, there is still scarce evidence on the prevalence of food poisoning among workers with subsistence jobs on the streets and sidewalks of cities and on the factors that influence its presentation. Objectives: To determine sociodemographic, labor, sanitary, and environmental conditions that influence the prevalence of food poisoning in informal workers in downtown Medellín, Colombia. Methods: This is a cross-sectional study using a workers' survey as the primary source. A total of 686 workers aged ≥18 years who had been working for ≥ 5 years were surveyed. An assisted survey was initially applied as a pilot test for training purposes and to obtain informed consent. Results: We identified several associations and explanatory factors of food poisoning using chi-square tests and prevalence ratios, with unadjusted and adjusted 95% confidence intervals (95%CI). A higher prevalence of food poisoning (p < 0.05) was observed in workers with lower frequency of waste collection (PR = 2.09; 95%CI = 1.04-4.19), who left cooked food (PR = 6.40; 95%CI = 2.34-17.8), beverages or chopped fruits uncovered at their workplace (PR = 3.92; 95%CI = 1.40-10.48), with inadequate waste management (PR = 4.84; 95%CI = 2.12-11.06), exposure to polluted water (PR = 3.00; 95%CI = 1.20-7.50) and acceptable water supply (PR = 5.40; 95%CI = 1.60-17.8). The factors that explained higher rates of food poisoning were not having a waste collection service (PRadjusted = 5.58; 95%CI = 3.38-13.10), inadequate waste management (PRadjusted = 6.61; 95%CI = 1.25-34.84), and having sanitary services next to worker's stall (PRadjusted = 14.44; 95%CI = 1.26-165.11). Conclusions: The conditions that are associated with and explain the higher prevalence of food poisoning in this working population can be addressed with health promotion and disease prevention interventions.

Introducción: Aunque se han realizado estudios con trabajadores informales en América Latina y el Caribe, aun es escasa la evidencia con respecto a la prevalencia de intoxicaciones alimentarias en trabajadores con empleos de subsistencia en las calles y aceras de las ciudades y a los factores que influyen en su presentación. Objetivos: Determinar las condiciones sociodemográficas, laborales, sanitarias y ambientales que influyen en la prevalencia de intoxicación alimentaria en trabajadores informales del centro de Medellín. Métodos: Estudio transversal con fuente primaria de información en un censo de 686 trabajadores, ≥18 años y con ≥5 años en su oficio. Se aplicó encuesta asistida previa realización de prueba piloto, estandarización de encuestadores y toma de consentimiento. Resultados: Se identificaron asociaciones y factores explicativos de intoxicación alimentaria, con pruebas del chi-cuadrado y razones de prevalencia (RP), con intervalos de confianza del 95% (IC95%) crudos y ajustados. Mayor prevalencia de intoxicación alimentaria (p < 0,05) en trabajadores con menor frecuencia de recolección de residuos (RP = 2,09; IC95% = 1,04-4,19), en quienes dejaban alimentos preparados (RP = 6,40; IC95% = 2,34-17,8), bebidas o fruta picada descubiertos en el puesto de trabajo (RP = 3,92; IC95% = 1,40-10,48), con inadecuado manejo de residuos (RP = 4,84; IC95% = 2,12-11,06), exposición a agua contaminada (RP = 3,00; IC95% = 1,20-7,50) y de aceptable calidad (RP = 5,40; IC95% = 1,60-17,8). Explicaron mayor intoxicación alimentaria no tener servicio de recolección de residuos (RPajustada = 5,58; IC95% = 3,38-13,10), inadecuado manejo de residuos (RPajustada = 6,61; IC95% = 1,25-34,84), y tener servicios sanitarios al lado del puesto de trabajo (RPajustada = 14,44; IC95% = 1,26-165,11). Conclusiones: Las condiciones que se asocian y explican mayor prevalencia de intoxicación alimentaria en esta población trabajadora, pueden ser revertidas con acciones de promoción de la salud y prevención de la enfermedad.

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BACKGROUND: Polymerization conditions affect the physical-mechanical properties of acrylic resins used for craniofacial prostheses. OBJECTIVE: The aim of this study was to evaluate the effect of microwave polymerization on the thermomechanical properties and surface morphology of ocular prostheses fabricated with polymethyl methacrylate (PMMA). METHODS: PMMA discs were polymerized with microwave energy and with conventional heat polymerization (CHP) method. Ocular prostheses were fabricated to determine whether there were changes according to the polymerization method. The surface morphology and roughness were observed under SEM and AFM. The Vickers Hardness number (VHN) and flexural strength were measured. Thermal properties were evaluated with TGA/DSC, and chemical composition with FTIR. RESULTS: The PMMA acrylic resin polymerized with microwave energy showed a smooth surface with some relief areas. In the internal surface of the ocular prosthesis with microwave energy the PMMA is more compact. The mean roughness values were higher and statistically significant with CHP (P < 0.05), while the surface hardness and flexural strength were higher with microwave energy (P < 0.05). CONCLUSION: There were no changes in the calorimetry with either method, TGA showed an exothermic peak around 120 °C with CHP method. PMMA polymerized with microwave energy improved the mechanical and surface properties of the ocular prostheses.

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The objective of this study is to compare the environmental and social performance of two small-scale avocado biorefineries implanted in a rural zone in the North of Colombia. Two small-scale biorefineries were proposed. Small-B1 addressed to produce avocado oil and animal feed, and Small-B2 focused on the guacamole production. The environmental analysis was done by applying the life cycle assessment methodology. Then, agronomic information and process simulation were required to complete the analysis. Moreover, the water footprint of the avocado crops was estimated. Both biorefineries were compared with the direct avocados production and commercialization. The social assessment was achieved by the estimation of quantitative indicators related to wages, jobs, and working hours. The agricultural carbon and water footprints of the creole avocado crop were 0.59 kg CO2-eq/kg and 2.13 m3/kg. In the same way, Small-B1 and Small-B2 obtained a carbon and water footprints of 8.99 kg CO2-eq/kg and 6.63 m3/kg and 0.72 kg CO2-eq/kg and 1.38 m3/kg, respectively. The hotspots of the creole avocado crop are related to the use of fertilizers and fungicides. Then, new strategies should be implemented to reduce the farmer's dependency. The social analysis exhibit a high resilience of the Small-B1 biorefinery since a salary increase to worker about 50% can be proposed. In addition, the installation of this biorefinery can create more than ten jobs. A disjunction was found between the economic, environmental, and social analyses. Thus, the need to establish a multidimensional strategy to design sustainable biorefineries is presented.

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In ecdysozoan animals, moulting entails the production of a new exoskeleton and shedding of the old one during ecdysis. It is induced by a pulse of ecdysone that regulates the expression of different hormonal receptors and activates a peptide-mediated signalling cascade. In Holometabola, the peptidergic cascade regulating ecdysis has been well described. However, very little functional information regarding the neuroendocrine regulation of ecdysis is available for Hemimetabola, which display an incomplete metamorphosis. We use Rhodnius prolixus as a convenient experimental model to test two hypotheses: (1) the role of neuropeptides that regulate ecdysis in Holometabola is conserved in hemimetabolous insects; and (2) the neuropeptides regulating ecdysis play a role in the regulation of female reproduction during the adult stage. The RNA interference-mediated reduction of ecdysis triggering hormone (ETH) mRNA levels in fourth-instar nymphs resulted in lethality at the expected time of ecdysis. Unlike in holometabolous insects, knockdown of eth and orcokinin isoform A (oka) did not affect oviposition in adult females, pointing to a different endocrine regulation of ovary maturation. However, eth knockdown prevented egg hatching. The blockage of egg hatching appears to be a consequence of embryonic ecdysis failure. Most of the first-instar nymphs hatched from the eggs laid by females injected with dsRNA for eclosion hormone (dsEH), crustacean cardioactive peptide (dsCCAP) and dsOKA died at the expected time of ecdysis, indicating the crucial involvement of these genes in post-embryonic development. No phenotypes were observed upon corazonin (cz) knockdown in nymphs or adult females. The results are relevant for evolutionary entomology and could reveal targets for neuropeptide-based pest control tools.

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Adaptability, heterogeneity, and plasticity are the hallmarks of macrophages. How these complex properties emerge from the molecular interactions is an open question. Thus, in this study we propose an actualized regulatory network of cytokines, signaling pathways, and transcription factors to survey the differentiation, heterogeneity, and plasticity of macrophages. The network recovers attractors, which in regulatory networks correspond to cell types, that correspond to M0, M1, M2a, M2b, M2c, M2d, M2-like, and IL-6 producing cells, including multiple cyclic attractors that are stable to perturbations. These cyclic attractors reproduce experimental observations and show that oscillations result from the structure of the network. We also study the effect of the environment in the differentiation and plasticity of macrophages, showing that the observed heterogeneity in macrophage populations is a result of the regulatory network and its interaction with the micro-environment. The macrophage regulatory network gives a mechanistic explanation to the heterogeneity and plasticity of macrophages seen in vivo and in vitro, and offers insights into the mechanism that allows the immune system to react to a complex dynamic environment.

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Process sustainability has been one of the most challenging issues faced by process designers. Conceptual designed processes do not overcome this stage because aspects such as context and technological readiness level are left aside. This paper proposes a strategy to consider different processing routes for biomass (compendium of existing routes) towards sustainable development. The strategy comprises five stages where a supported bioprocesses selection is made by considering the chemical composition of the raw material and the context where biomass is produced and processed. This strategy aims to give decision tools to designers to filter and reduce the number of options to be considered when proposing an alternative biomass use. The proposed strategy was applied to upgrade orange peel waste and sugarcane bagasse to demonstrate how it can be applied. In conclusion, selecting of bioprocesses and considering the proposed strategycould improve the biorefineries design. Even so, more bioprocesses must be included.

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In this model we use a dynamic and multistable Boolean regulatory network to provide a mechanistic explanation of the lymphopenia and dysregulation of CD4+ T cell subsets in COVID-19 and provide therapeutic targets. Using a previous model, the cytokine micro-environments found in mild, moderate, and severe COVID-19 with and without TGF-ß and IL-10 was we simulated. It shows that as the severity of the disease increases, the number of antiviral Th1 cells decreases, while the the number of Th1-like regulatory and exhausted cells and the proportion between Th1 and Th1R cells increases. The addition of the regulatory cytokines TFG-ß and IL-10 makes the Th1 attractor unstable and favors the Th17 and regulatory subsets. This is associated with the contradictory signals in the micro-environment that activate SOCS proteins that block the signaling pathways. Furthermore, it determined four possible therapeutic targets that increase the Th1 compartment in severe COVID-19: the activation of the IFN-γ pathway, or the inhibition of TGF-ß or IL-10 pathways or SOCS1 protein; from these, inhibiting SOCS1 has the lowest number of predicted collateral effects. Finally, a tool is provided that allows simulations of specific cytokine environments and predictions of CD4 T cell subsets and possible interventions, as well as associated secondary effects.

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This research paper seeks to evaluate the influence of the context, processing scale, and portfolio of products on the economic performance of different avocado-based biorefineries. For this, two scenarios in small and large-scale biorefineries were compared. The case of scenario 1 (avocado oil, animal feed, and electricity production) was the best small-scale alternative to be implemented in rural zones than scenario 2 (guacamole and electricity production). The minimum Processing Scale for Economic Feasibility was 0.85 and 1.1 ton/day for scenarios 1 and 2. Compared to lactic acid and xylitol production, the large-scale process addressed to produce levulinic acid, furfural, and lignin (scenario 1) was the best option (scenario 2). In scenario 1, the minimum Processing Scale for Economic Feasibility was 15.50 ton/day compared with scenario 2 of 41.95 ton/day. Based on these values, scenario 1 has the highest feasibility of being implemented in countries such as Colombia.

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INTRODUCTION: Chagas disease (CD) is caused by Trypanosoma cruzi. When acquired, the disease develops in stages. For diagnosis, laboratory confirmation is required, and an extensive assessment of the patient's health should be performed. Treatment consists of the administration of trypanocidal drugs, which may cause severe adverse effects. The objective of our systematic review was to analyze data contained in the CD published case reports to understand the challenges that patients and clinicians face worldwide. MATERIALS AND METHODS: We performed a systematic review following the PRISMA guidance. PubMed database was explored using the terms 'American trypanosomiasis' or 'Chagas disease'. Results were limited to human case reports written in English or Spanish. A total of 258 reports (322 patients) were included in the analysis. Metadata was obtained from each article. Following this, it was analyzed to obtain descriptive measures. RESULTS: From the sample, 56.2% were males and 43.8% were females. Most cases were from endemic countries (85.4%). The most common clinical manifestations were fever during the acute stage (70.0%), dyspnea during the chronic stage in its cardiac form (53.7%), and constipation during the chronic stage in its digestive form (73.7%). Most patients were diagnosed in the chronic stage (72.0%). Treatment was administered in 56.2% of cases. The mortality rate for the acute stage cases was 24.4%, while for the chronic stage this was 28.4%. DISCUSSION: CD is a parasitic disease endemic to Latin America, with increasing importance due to human and vector migration. In this review, we report reasons for delays in diagnosis and treatment, and trends in medical practices. Community awareness must be increased to improve CD's diagnoses; health professionals should be appropriately trained to detect and treat infected individuals. Furthermore, public health policies are needed to increase the availability of screening and diagnostic tools, trypanocidal drugs, and, eventually, vaccines.

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SUMMARY: In patients with mesial temporal lobe epilepsy, high-frequency, low-amplitude electrical stimulation (ES) was applied during 3 weeks through contacts of intracranial electrodes that defined the epileptogenic zone. This subacute ES induced cessation of spontaneous seizures, decreased the number of EEG interictal spikes, caused a 10-fold increase in threshold to induce postdischarges, and showed a profound decrease in regional blood flow of the stimulated area in SPECT studies. Autoradiography analysis of surgical specimens from these patients demonstrated increased expression of benzodiazepine receptors and in gamma-aminobutyric acid content, particularly in the parahippocampal cortex. These observations provided evidence of a gamma-aminobutyric acid-mediated antiepileptic effect induced by ES. Several reports of long-term hippocampal ES through internalized neurostimulators have confirmed the antiepileptic effect on mesial temporal lobe-initiated seizures, with preservation of neuropsychological performance, in particular memory functions. The experience of the authors is that the response is optimal in patients without hippocampal sclerosis evidenced by MRI, whereas it is less significant and delayed in patients with hippocampal sclerosis. Other studies reported the best result stimulating through the contacts in the subiculum, the transition between the hippocampus and parahippocampal cortex, that usually escapes to the hippocampal sclerosis. Currently, the effect of ES directed at the subiculum and the parahippocampal cortex in patients with hippocampal sclerosis is under investigation.

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