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As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC).

Climate changes with global warming associated with rising atmospheric [CO2] can strongly impact crop performance, including coffee, which is one of the most world’s traded agricultural commodities. Therefore, it is of utmost importance to understand the mechanisms of heat tolerance and the potential role of elevated air CO2 (eCO2) in the coffee plant response, particularly regarding the antioxidant and other protective mechanisms, which are crucial for coffee plant acclimation. For that, plants of Coffea arabica cv. Geisha 3, cv. Marsellesa and their hybrid (Geisha 3 × Marsellesa) were grown for 2 years at 25/20 °C (day/night), under 400 (ambient CO2, aCO2) or 700 µL (elevated CO2, eCO2) CO2 L−1, and then gradually submitted to a temperature increase up to 42/30 °C, followed by recovery periods of 4 (Rec4) and 14 days (Rec14). Heat (37/28 °C and/or 42/30 °C) was the major driver of the response of the studied protective molecules and associated genes in all genotypes. That was the case for carotenoids (mostly neoxanthin and lutein), but the maximal (α + β) carotenes pool was found at 37/28 °C only in Marsellesa. All genes (except VDE) encoding for antioxidative enzymes (catalase, CAT; superoxide dismutases, CuSODs; ascorbate peroxidases, APX) or other protective proteins (HSP70, ELIP, Chape20, Chape60) were strongly up-regulated at 37/28 °C, and, especially, at 42/30 °C, in all genotypes, but with maximal transcription in Hybrid plants. Accordingly, heat greatly stimulated the activity of APX and CAT (all genotypes) and glutathione reductase (Geisha3, Hybrid) but not of SOD. Notably, CAT activity increased even at 42/30 °C, concomitantly with a strongly declined APX activity. Therefore, increased thermotolerance might arise through the reinforcement of some ROS-scavenging enzymes and other protective molecules (HSP70, ELIP, Chape20, Chape60). Plants showed low responsiveness to single eCO2 under unstressed conditions, while heat promoted changes in aCO2 plants. Only eCO2 Marsellesa plants showed greater contents of lutein, the pool of the xanthophyll cycle components (V + A + Z), and β-carotene, compared to aCO2 plants at 42/30 °C. This, together with a lower CAT activity, suggests a lower presence of H2O2, likely also associated with the higher photochemical use of energy under eCO2. An incomplete heat stress recovery seemed evident, especially in aCO2 plants, as judged by the maintenance of the greater expression of all genes in all genotypes and increased levels of zeaxanthin (Marsellesa and Hybrid) relative to their initial controls. Altogether, heat was the main response driver of the addressed protective molecules and genes, whereas eCO2 usually attenuated the heat response and promoted a better recovery. Hybrid plants showed stronger gene expression responses, especially at the highest temperature, when compared to their parental genotypes, but altogether, Marsellesa showed a greater acclimation potential. The reinforcement of antioxidative and other protective molecules are, therefore, useful biomarkers to be included in breeding and selection programs to obtain coffee genotypes to thrive under global warming conditions, thus contributing to improved crop sustainability.

La displasia septo-óptica (DSO) es una entidad que incluye hipoplasia de nervios ópticos, disgenesia de la línea media cerebral y disfunción hipotálamo-hipofisaria. Entre las teorías sobre su patogenia es de resaltar una posible disrupción vascular que altera el desarrollo de las estructuras involucradas. Dado que la (DSO) es una patología infrecuente, se presenta el caso de un recién nacido que desde sus controles prenatales presentó alteraciones anatómicas cerebrales en línea media. Posteriormente al nacimiento se confirmaron las siguientes: ausencia de septum pellucidum, dilatación ventricular supratentorial con sospecha de estenosis acueductal y disgenesia del cuerpo calloso, además de una trombosis de seno venoso. Se resalta la importancia de mostrar la relación de estas dos patologías puesto que solamente encontramos otro caso reportado en la literatura. Igualmente, se destacan herramientas del manejo de trombosis cerebral neonatal. Por último, se resalta la utilidad de los controles prenatales como guía del enfoque rápido para el diagnóstico en este paciente.

This study aimed to assess the efficiency of Ca enrichment in tubers of three genotypes of Solanum tuberosum L., through foliar spraying with CaCl2 and Ca(NO3)2 solutions. In this context, soil heterogeneity of three potato-growing fields, as well as the implications of Ca accumulation among tissues and some quality parameters were assessed. Three potato varieties (Agria, Picasso and Rossi) were grown in three production fields and during the life cycle, four pulverizations with calcium chloride (3 and 6 kg ha−1) or calcium nitrate (0.5, 2 and 4 kg ha−1) were applied. For screening the potential phytotoxicity, using Agria as a test system, the potential synthesis of photoassimilates was determined, and it was found that after the 3rd Ca application, leaf gas exchanges were moderately (net photosynthesis), to strongly (stomatal conductance) affected, although without impact on Ca accumulation in tubers. At harvest, the average Ca biofortification index varied between 5–40%, 40–35% and 4.3–13% in Agria, Picasso and Rossi, respectively. Moreover, the equatorial region of the tubers in general showed that Ca accumulation prevailed in the epidermis and, in some cases, in inner areas of the potato tubers. Biofortified tubers with Ca also showed some significant changes in total soluble solids and colorimetric parameters. It is concluded that Ca enrichment of potato tubers through foliar spraying complemented the xylem mass flow of Ca from roots, through phloem redistribution. Both fertilizers showed similar efficiency, but Rossi revealed a lower index of Ca accumulation, eventually due to different metabolic characteristics. Although affected by Ca enrichment, potato tubers maintained a high quality for industrial processing.

Objetivo: describir las tasas de incidencia de las infecciones asociadas a la atención en salud relacionadas con dispositivos, presentadas en la unidad de recién nacidos de un hospital universitario de la ciudad de Bogotá, Colombia. Materiales y métodos:estudio observacional descriptivo de corte transversal de periodo. Se incluyeron 83 pacientes con 84 infecciones asociadas a la atencion en salud asociadas a dispositivo hospitalizados en el Hospital Universitario San Ignacio del 2011 al 2020.Resultados: el 59.3% de los pacientes (n=50) eran pacientes pretermino, de sexo masculino (61,9%; n=52). La IAAS más frecuente fue la infección del torrente sanguíneo asociada a catéter (89,2%; n=75) con una tasa de incidencia de 1,5 a 6,3 por 1000 días catéter, siendo el Staphylococcus epidermidis el microorganismo más común (78,7%). La neumonía asociada al ventilador producida por el Staphylococcus Aureus meticilino resistente (50%) con una tasa de incidencia del 5,3 al 6,3 por 1000 días de ventilador, ocupó el segundo lugar, y la infección de vías urinarias asociada a catéter vesical con una tasa de incidencia de 1,5 a 9,5 por 1000 días catéter, fue la tercera en frecuencia. Discusión: las tasas de incidencia de la unidad neonatal son comparables con las tasas de incidencia nacionales, por debajo de las reportadas por la INICC y por encima de las reportadas por la NHSN. Las estrategias de prevención son una herramienta para la disminución de las tasas de incidencia.Conclusión: las tasas de incidencia de las IAAS relacionadas con dispositivo fueron mayores en los recién nacidos pretérmino, y las estrategias de prevención son un desafío para disminuir la morbimortalidad asociada.

Continuing with our program to obtain new histamine H3 receptor (H3R) ligands, in this work we present the synthesis, H3R affinity and in silico studies of a series of eight new synthetically accessible purine derivatives. These compounds are designed from the isosteric replacement of the scaffold presented in our previous ligand, pyrrolo[2,3-d]pyrimidine ring, by a purine core. This design also considers maintaining the fragment of bipiperidine at C-4 and aromatic rings with electron-withdrawing groups at N-9, as these fragments are part of the proposed pharmacophore. The in vitro screening results show that two purine derivatives, 3d and 3h, elicit high affinities to the H3R (Ki values of 2.91 and 5.51 nM, respectively). Both compounds are more potent than the reference drug pitolisant (Ki 6.09 nM) and show low toxicity with in vitro models (IC50 > 30 µM on HEK-293, SH-SY5Y and HepG2 cell lines). Subsequently, binding modes of these ligands are obtained using a model of H3R by docking and molecular dynamics studies, thus determining the importance of the purine ring in enhancing affinity due to the hydrogen bonding of Tyr374 to the N-7 of this heterocycle. Finally, in silico ADME properties are predicted, which indicate a promising future for these molecules in terms of their physical–chemical properties, absorption, oral bioavailability and penetration in the CNS.

Introducción: La infección respiratoria aguda (IRA) es un grupo heterogéneo de patologías respiratorias de etiología viral y bacteriana que incluye Chlamydophila pneumoniae (CP) y Mycoplasma pneumoniae (MP), que no son identificados de manera rutinaria, y en el adulto mayor presentan tasas de mortalidad 3-5 veces mayores que las registradas en otros grupos etarios. Metodología: Estudio prospectivo para determinar la proporción de patógenos bacterianos atípicos en los adultos mayores con IRA, en Bogotá. El diagnóstico microbiológico se determinó mediante PCR en tiempo real (qPCR) en muestras de origen respiratorio y serología para anticuerpos IgG, IgA e IgM frente a MP y CP. Resultados: Un total de 71 pacientes fueron incluidos entre 2012 y 2013. Las infecciones respiratorias superiores fueron diagnosticadas en el 69 % de los pacientes y las infecciones del tracto respiratorio inferior en un 31 %. MP fue identificado en el 9,8 % y el 8,5 % en CP. Conclusiones: Estos resultados indican que CP y MP son agentes etiológicos importantes de infecciones respiratorias agudas en los adultos mayores en Bogotá.

The understanding of acclimation strategies to low temperature and water availability is decisive to ensure coffee crop sustainability, since these environmental conditions determine the suitability of cultivation areas. In this context, the impacts of single and combined exposure to drought and cold were evaluated in three genotypes of the two major cropped species, Coffea arabica cv. Icatu, Coffea canephora cv. Apoatã, and the hybrid Obatã. Crucial traits of plant resilience to environmental stresses have been examined: photosynthesis, lipoperoxidation and the antioxidant response. Drought and/or cold promoted leaf dehydration, which was accompanied by stomatal and mesophyll limitations that impaired leaf C-assimilation in all genotypes. However, Icatu showed a lower impact upon stress exposure and a faster and complete photosynthetic recovery. Although lipoperoxidation was increased by drought (Icatu) and cold (all genotypes), it was greatly reduced by stress interaction, especially in Icatu. In fact, although the antioxidative system was reinforced under single drought and cold exposure (e.g., activity of enzymes as Cu,Zn-superoxide dismutase, ascorbate peroxidase, APX, glutathione reductase and catalase, CAT), the stronger increases were observed upon the simultaneous exposure to both stresses, which was accompanied with a transcriptional response of some genes, namely related to APX. Complementary, non-enzyme antioxidant molecules were promoted mostly by cold and the stress interaction, including α-tocopherol (in C. arabica plants), ascorbate (ASC), zeaxanthin, and phenolic compounds (all genotypes). In general, drought promoted antioxidant enzymes activity, whereas cold enhanced the synthesis of both enzyme and non-enzyme antioxidants, the latter likely related to a higher need of antioxidative capability when enzyme reactions were probably quite repressed by low temperature. Icatu showed the wider antioxidative capability, with the triggering of all studied antioxidative molecules by drought (except CAT), cold, and, particularly, stress interaction (except ASC), revealing a clear stress cross-tolerance. This justified the lower impacts on membrane lipoperoxidation and photosynthetic capacity under stress interaction conditions, related to a better ROS control. These findings are also relevant to coffee water management, showing that watering in the cold season should be largely avoided.