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Gastrointestinal (GI) toxicity is a common side effect in patients undergoing oxaliplatin (OxPt)-based chemotherapy for colorectal cancer (CRC). Frequently, this complication persists in the long term and could affect the efficacy of the treatment and the patient’s life quality. This long-term GI toxicity is thought to be related to OxPt-induced enteral neuropathy. AmotL2 is a member of the Angiomotin family of proteins, which play a role in cell survival, neurite outgrowth, synaptic maturation, oxidative stress protection, and inflammation. In order to assess the role of AmotL2 in OxPt-induced enteral neuropathy, we studied the expression of AmotL2 in cells of the enteric nervous system (ENS) of untreated and OxPt-treated CRC patients and its relationship with inflammation, using immunofluorescence confocal microscopy. Our results in human samples show that the total number of neurons and glial cells decreased in OxPt-treated patients, and TNF-α and AmotL2 expression was increased and colocalized in both neurons and glia. AmotL2 differential expression between OxPt-treated and untreated CRC patients shows the involvement of this scaffold protein in the inflammatory component and toxicity by OxPt in the ENS.

Abstract Background Endothelial colony forming cells (ECFCs), alone or in combination with mesenchymal stem cells, have been selected as potential therapeutic candidates for critical limb-threatening ischemia (CLTI), mainly for those patients considered as “no-option,” due to their capability to enhance revascularization and perfusion recovery of ischemic tissues. Nevertheless, prior to translating cell therapy to the clinic, biodistribution assays are required by regulatory guidelines to ensure biosafety as well as to discard undesired systemic translocations. Different approaches, from imaging technologies to qPCR-based methods, are currently applied. Methods In the current study, we have optimized a cell-tracking assay based on DiR fluorescent cell labeling and near-infrared detection for in vivo and ex vivo assays. Briefly, an improved protocol for DiR staining was set up, by incubation of ECFCs with 6.67 µM DiR and intensive washing steps prior cell administration. The minimal signal detected for the residual DiR, remaining after these washes, was considered as a baseline signal to estimate cell amounts correlated to the DiR intensity values registered in vivo. Besides, several assays were also performed to determine any potential effect of DiR over ECFCs functionality. Furthermore, the optimized protocol was applied in combination with qPCR amplification of specific human Alu sequences to assess the final distribution of ECFCs after intramuscular or intravenous administration to a murine model of CLTI. Results The optimized DiR labeling protocol indicated that ECFCs administered intramuscularly remained mainly within the hind limb muscle while cells injected intravenously were found in the spleen, liver and lungs. Conclusion Overall, the combination of DiR labeling and qPCR analysis in biodistribution assays constitutes a highly sensitive approach to systemically track cells in vivo. Thereby, human ECFCs administered intramuscularly to CLTI mice remained locally within the ischemic tissues, while intravenously injected cells were found in several organs. Our data corroborate the need to perform biodistribution assays in order to define specific parameters such as the optimal delivery route for ECFCs before their application into the clinic.

This study explores an eco-friendly method for recovering platinum group metals from a synthetic automotive three-way catalyst (TWC). Bioleaching of palladium (Pd) using the thiosulfate-copper-ammonia leaching processes, with biogenic thiosulfate sourced from a bioreactor used for biogas biodesulfurization, is proposed as a sustainable alternative to conventional methods. Biogenic thiosulfate production was optimized in a gas-lift bioreactor by studying the pH (8–10) and operation modes (batch and continuous) under anoxic and microaerobic conditions for 35 d. The maximum concentration of 4.9 g S2O32− L−1 of biogenic thiosulfate was reached under optimal conditions (batch mode, pH = 10, and airflow rate 0.033 vvm). To optimize Pd bioleaching from a ground TWC, screening through a Plackett–Burman design determined that oxygen and temperature significantly affected the leaching yield negatively and positively, respectively. Based on these results, an optimization through an experimental design was performed, indicating the optimal conditions to be Na2S2O3 1.2 M, CuSO4 0.03 M, (NH4)2SO4 1.5 M, Na2SO3 0.2 M, pH 8, and 60 °C. A remarkable 96.2 and 93.2% of the total Pd was successfully extracted from the solid at 5% pulp density using both commercially available and biogenic thiosulfate, highlighting the method’s versatility for Pd bioleaching from both thiosulfate sources.

Abstract Objective Main malaria diagnosis is based on microscopic examination combined with rapid diagnostic tests. Both methods have low sensitivity and specificity. Loop-mediated isothermal amplification techniques have shown a sensitivity similar to PCR but with lower times of performance. This study aimed to assess a commercial LAMP for the diagnosis of malaria (Alethia® Malaria) against the Nested-Multiplex-Malaria PCR, including the analytical sensitivity and the operational characteristics. Results One hundred five samples out of 114 rendered valid results, obtaining 85 positive samples and 18 negative samples with an agreement of 98% compared to the reference method with a sensitivity, specificity and kappa coefficient of 98.84%, 94.74% and 0.94 respectively, with only two discrepant samples. The turnaround time was estimated in 1 h and 30 min, with a cost of 32.67€ per determination. The results showed several advantages of the Alethia ® Malaria, as it was easy to perform, minimal training requirement and 40 min run. Moreover, it includes an internal control to avoid false negatives. However, it also showed some limitations such as the need for a specific amplification and detection device, the detection of only Plasmodium spp. and a very high price.

Abstract COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p

Gastrointestinal (GI) toxicity is a common side effect in patients undergoing oxaliplatin (OxPt)-based chemotherapy for colorectal cancer (CRC). Frequently, this complication persists in the long term and could affect the efficacy of the treatment and the patient's life quality. This long-term GI toxicity is thought to be related to OxPt-induced enteral neuropathy. AmotL2 is a member of the Angiomotin family of proteins, which play a role in cell survival, neurite outgrowth, synaptic maturation, oxidative stress protection, and inflammation. In order to assess the role of AmotL2 in OxPt-induced enteral neuropathy, we studied the expression of AmotL2 in cells of the enteric nervous system (ENS) of untreated and OxPt-treated CRC patients and its relationship with inflammation, using immunofluorescence confocal microscopy. Our results in human samples show that the total number of neurons and glial cells decreased in OxPt-treated patients, and TNF-α and AmotL2 expression was increased and colocalized in both neurons and glia. AmotL2 differential expression between OxPt-treated and untreated CRC patients shows the involvement of this scaffold protein in the inflammatory component and toxicity by OxPt in the ENS. [ABSTRACT FROM AUTHOR]

BackgroundInterleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.MethodsSecondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.ResultsA total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.ConclusionIn those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Background: The determination of kinetic parameters and the development of mathematical models are of great interest to predict the growth of microalgae, the consumption of substrate and the design of photobioreactors focused on CO2 capture. However, most of the models in the literature have been developed for CO2 concentrations below 10%. Results: A nonaxenic microalgal consortium was isolated from landfill leachate in order to study its kinetic behavior using a dynamic model. The model considered the CO2 mass transfer from the gas phase to the liquid phase and the effect of light intensity, assimilated nitrogen concentration, ammonium concentration and nitrate concentration. The proposed mathematical model was adjusted with 13 kinetic parameters and validated with a good fit obtained between experimental and simulated data. Conclusions: Good results were obtained, demonstrating the robustness of the proposed model. The assumption in the model of DIC inhibition in the ammonium and nitrate uptakes was correct, so this aspect should be considered when evaluating the kinetics with microalgae with high inlet CO2 concentrations. Keywords: Dynamic model, Nonaxenic consortium, Photon flux density, Mass transfer, Leachate, Landfill, Ammonium, Nitrate, Carbon dioxide

A pilot-scale biotrickling filter (BTF) was operated in counter-current flow mode under anoxic conditions, using diluted agricultural digestate as inoculum and as the recirculation medium for the nutrient source. The process was tested on-site at an agricultural fermentation plant, where real biogas was used. The pilot plant was therefore exposed to real process-related fluctuations. The purpose of this research was to attest the validity of the filtration process for use at an industrial-scale by operating the pilot plant under realistic conditions. Neither the use of agricultural digestate as trickling liquid and nor a BTF of this scale have previously been reported in the literature. The pilot plant was operated for 149 days. The highest inlet load was 8.5 gS-H2Sm−3h−1 with a corresponding removal efficiency of 99.2%. The pH remained between 7.5 and 4.6 without any regulation throughout the complete experimental phase. The analysis of the microbial community showed that both anaerobic and anoxic bacteria can adapt to the fluctuating operating conditions and coexist simultaneously, thus contributing to the robustness of the process. The operation of an anoxic BTF with agricultural digestate as the trickling liquid proved to be viable for industrial-scale use.

La lactancia materna exclusiva (LME) aporta diversos beneficios a la salud del niño y de la madre. La Teoría de la Conducta Planeada (TCP) es un modelo enfocado en la predicción de algunas conductas relacionadas con la salud, como la LME. Elobjetivo de este estudio fue identificar la relación de las variables de la TCP con la intención de dar LME. Se llevó a cabo un estudio transversal con 442 mujeres embarazadas de la Ciudad de México. Las variables de la TCP se midieron con instrumentos previamente validados. Un análisis de regresión logística múltiple, ajustado por paridad y edad materna, identificó asociaciones significativas entre la intención de amamantar y la norma subjetiva, OR = 1.07 (IC 95% [1.01, 1.14]), y el control conductual percibido, OR = 1.05 (IC 95% [1.01, 1.11]), con la intención. Como conclusión, en esta muestra se asociaron dos constructos de la TCP con la intención de lactar de forma exclusiva.

Este artículo tiene como objetivo describir los principales desafíos que enfrenta El Salvador en materia de políticas educativas, especialmente las que han sido diseñadas para contrarrestar las altas tasas de abandono o deserción escolar, y la recaptura de la población de jóvenes que podrían retomar sus estudios para obtener su Bachillerato (Enseñanza Secundaria completa) y, a la vez, dotarse de mayores y mejores herramientas para enfrentar el futuro con alguna calificación ocupacional o laboral. Se describe la situación social, económica y educacional del país y también de su entorno internacional, y se muestra parte de la arquitectura general del rediseño curricular, de gestión y financiamiento para las denominadas Modalidades Flexibles (en adelante MF), una alternativa a la educación regular, para aumentar su cobertura. Las MF nacen con el Plan de Educación 2021 (del año 2005), pero no ha logrado los resultados esperados, especialmente en cobertura y calidad. El Proyecto ECYP (Education for Children and Young Project) tiene entre sus objetivos rediseñar y actualizar las MF para ampliar significativamente su, hasta ahora, escasa cobertura y calidad, agregándole, además, los componentes de habilidades para la vida y una formación técnico-laboral para el ingreso de los estudiantes al mercado laboral si así lo prefieren. El autor de este artículo descriptivo se desempeña actualmente, en cuanto consultor internacional, como coordinador del proyecto de rediseño del currículo, el financiamiento y la gestión de las MF, un proyecto financiado por la Agencia de los Estados Unidos para el Desarrollo Internacional (USAID), a través de la Fundación para la Educación Integral Salvadoreña (FEDISAL).

Four oceanographic cruises were carried out between April 2011 and May 2013 on the continental slope of the southern Gulf of Mexico (GoM) in a depth range of 290 to 1200 m on board the R/V JUSTO SIERRA. A total of 91 trawls covered a total swept area of 170.49 hectares. We recorded 177 fish species belonging to 80 families. Fifteen species extended their distribution into the south of the gulf and 37 increased their depth ranges. Five species could have commercial importance: Aphanopus carbo Lowe, 1839; Hydrolagus mirabilis (Collett, 1904); Helicolenus dactylopterus (Delaroche, 1809); Lophius gastrophysus Miranda Ribeiro, 1915, and Merluccius albidus (Mitchill, 1818). The most abundant species were Polymixia lowei Günther, 1859; Parasudis truculenta (Goode & Bean, 1896); M. albidus, Chlorophthalmus agassizi Bonaparte, 1840; Dibranchus atlanticus Peters, 1876; Nezumia aequalis (Günther, 1878); Yarrella blackfordi Goode & Bean, 1896; and Laemonema barbatulum Goode & Bean, 1883. High values of fish species richness, diversity, and evenness were registered throughout the study area. A high percentage of the fish species (97%) collected during this project are distributed in the entire GoM. Most of the species showed a wide depth distribution; however, a vertical zonation of species can be observed.

Background: Bone Marrow Mononuclear Cells (BM-MNC) constitute a promising alternative for the treatment of Chronic Limb-Threatening ischemia (CLTI), a disease characterized by extensive blockade of peripheral arteries, clinically presenting as excruciating pain at rest and ischemic ulcers which may lead to gangrene and amputation. BM-MNC implantation has shown to be efficient in promoting angiogenesis and ameliorating ischemic symptoms in CLTI patients. However, the variability seen between clinical trials makes necessary a further understanding of the mechanisms of action of BM-MNC, and moreover, to improve trial characteristics such as endpoints, inclusion/exclusion criteria or drug product compositions, in order to implement their use as stem-cell therapy.Materials: Herein, the effect of REX-001, a human-BM derived cell suspension enriched for mononuclear cells, granulocytes and CD34+ cells, has been assessed in a murine model of CLTI. In addition, a REX-001 placebo solution containing BM-derived red blood cells (BM-RBCs) was also tested. Thus, 24 h after double ligation of the femoral artery, REX-001 and placebo were administrated intramuscularly to Balb-c nude mice (n:51) and follow-up of ischemic symptoms (blood flow perfusion, motility, ulceration and necrosis) was carried out for 21 days. The number of vessels and vascular diameter sizes were measured within the ischemic tissues to evaluate neovascularization and arteriogenesis. Finally, several cell-tracking assays were performed to evaluate potential biodistribution of these cells.Results: REX-001 induced a significant recovery of blood flow by increasing vascular density within the ischemic limbs, with no cell translocation to other organs. Moreover, cell tracking assays confirmed a decrease in the number of infused cells after 2 weeks post-injection despite on-going revascularization, suggesting a paracrine mechanism of action.Conclusion: Overall, our data supported the role of REX-001 product to improve revascularization and ischemic reperfusion in CLTI.

BackgroundCell therapies and derived products have a high potential in aiding tissue and organ repairing and have therefore been considered as potential therapies for treating renal diseases. However, few studies have evaluated the impact of these therapies according to the stage of chronic kidney disease. The aim of this study was to evaluate the renoprotective effect of murine bone marrow mesenchymal stromal cells (BM-MSCs), their extracellular vesicles (EVs) and EVs-depleted conditioned medium (dCM) in an aggressive mouse model of chronic cyclosporine (CsA) nephrotoxicity in a preventive and curative manner.MethodsAfter 4 weeks of CsA-treatment (75 mg/kg daily) mice developed severe nephrotoxicity associated with a poor survival rate of 25%, and characterized by tubular vacuolization, casts, and cysts in renal histology. BM-MSC, EVs and dCM groups were administered as prophylaxis or as treatment of CsA nephrotoxicity. The effect of the cell therapies was analyzed by assessing renal function, histological damage, apoptotic cell death, and gene expression of fibrotic mediators.ResultsCombined administration of CsA and BM-MSCs ameliorated the mice survival rates (6–15%), but significantly renal function, and histological parameters, translating into a reduction of apoptosis and fibrotic markers. On the other hand, EVs and dCM administration were only associated with a partial recovery of renal function or histological damage. Better results were obtained when used as treatment rather than as prophylactic regimen i.e., cell therapy was more effective once the damage was established.ConclusionIn this study, we showed that BM-MSCs induce an improvement in renal outcomes in an animal model of CsA nephrotoxicity, particularly if the inflammatory microenvironment is already established. EVs and dCM treatment induce a partial recovery, indicating that further experiments are required to adjust timing and dose for better long-term outcomes.

Valentín Martínez-Otero (2019). Educación y diversidad cultural. Madrid: Editorial CCS, 140 páginas. ISBN: 978-84-9023-958-2 La actitud aproximativa hacia los otros “diferentes” o considerados como tales, queda favorecida en los ambientes donde se cultiva la cordialidad, un imperativo de convivencia, algo que se reivindica desde las páginas de este libro, en el que, de un modo u otro, todos los temas en él abordados convergen en un horizonte impulsor de convivencia, que ayudan a orientar significativamente a los estudiantes y profesores de las distintas carreras relacionadas con Educación, especialmente en lo que se refiere a relevantes aspectos teóricos de alcance práctico...

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins’ gene expression.

Aquaculture offers great potential for fish production in Lake Chapala, but reports of heavy metal contamination in fish have identified a main concern for this activity. In the present study, cultures of the species Cyprinus carpio and Ictalurus punctatus were grown in a net cage in Lake Chapala. The patterns of heavy metal accumulation (Cu, Zn, Cd, Hg, Pb, As) in muscle and liver were monitored in order to evaluate the level of metal incorporation in the fish. Estimates of weekly metal intake (EWI) were made based on the results of the concentrations in edible parts of fish of commercial size. The patterns of metal bioaccumulation between tissues and species showed that liver had a higher concentrating capacity for Zn, Cu, Cd, and Pb. In contrast, similar concentrations of Hg and As were found in the liver and muscle tissue. According to the EWI estimates, the heavy metals in these cultured fish do not represent a risk for human consumption.

Malaria is a parasitic disease distributed in tropical areas but with a high number of imported cases in non-endemic countries. The most specific and sensitive malaria diagnostic methods are PCR and LAMP. However, both require specific equipment, extraction procedures and a cold chain. This study aims to solve some limitations of LAMP method with the optimization and validation of six LAMP assays, genus and species-specific, using an easy and fast extraction method, the incorporation of a reaction control assay, two ways (Dual) of result reading and reagent lyophilization. The Dual-LAMP assays were validated against the Nested-Multiplex Malaria PCR. A conventional column and saline extraction methods, and the use of lyophilized reaction tubes were also assessed. A new reaction control Dual-LAMP-RC assay was designed. Dual-LAMP-Pspp assay showed no cross-reactivity with other parasites, repeatability and reproducibility of 100%, a significant correlation between parasite concentration and time to amplification and a LoD of 1.22 parasites/µl and 5.82 parasites/µl using column and saline extraction methods, respectively. Sensitivity and specificity of the six Dual-LAMP assays reach values of 100% or close to this, being lower for the Dual-LAMP-Pm. The Dual-LAMP-RC assay worked as expected. Lyophilized Dual-LAMP results were concordant with the reference method. Dual-LAMP malaria assays with the addition of a new reaction control LAMP assay and the use of a fast and easy saline extraction method, provided low limit of detection, no cross-reactivity, and good sensitivity and specificity. Furthermore, the reagent lyophilization and the dual result reading allow their use in most settings. [ABSTRACT FROM AUTHOR]

Este artículo trae nuevamente a colación el tema de la relación entre la calidad de la educación y la estructura socioeconómica y cultural en países como Chile y otras naciones latinoamericanas, donde parece persistir la creencia de que en la mejora del sistema de enseñanza se juega la casi totalidad de los problemas sociales (injusticia y desigualdad), económicos (concentración de los ingresos) y culturales del país. Es decir, la opinión de que el desarrollo de una sociedad más justa e igualitaria depende, casi sin contrapeso, de la mejora de la enseñanza y de un incremento en la financiación del sistema educativo. Este planteamiento suele manifestarse en declaraciones gubernamentales y no gubernamentales, y tiende a primar también en la opinión del ciudadano común y corriente, quien, a fuerza de un discurso mediático sostenido, termina creyendo que toda la responsabilidad del subdesarrollo, de la injusticia social y de la pobreza recae necesariamente sobre la educación y, principalmente, sobre los maestros, que son quienes trabajan en ella más directamente.

This Special Issue contains three articles and two reviews. The biological reactors used in the studies were fed with real biogas from Landfill or STPs. One research article concerns the use of a pilot scale plant with a combined process with a chemical and biological system. The other two studies concern anoxic biotrickling filters, with one study focused on the study of variable operation and its optimization through the response surface methodology, and the other focused on the selection of packing material. The reviews concern the current state of biogas desulfurization technologies, including an economic analysis, and the microbial ecology in biofiltration units. This Issue highlights some of the most relevant aspects about biogas desulfurization.