Targeting Several Biologically Reported Targets of Glioblastoma Multiforme by Assaying 2D and 3D Cultured Cells.

Glioblastoma multiforme (GBM) is account for 70% of all primary malignancies of the central nervous system. The median survival of human patients after treatment is around 15 months. There are several biological targets which have been reported that can be pursued using ligands with varied structures to treat this disease. In our group, we have developed several ligands that target a wide range of proteins involved in anticancer effects, such as histone deacetylase (HDACs), G protein-coupled estrogen receptor 1 (GPER), estrogen receptor-beta (ERß) and NADPH oxidase (NOX), that were screened on bidimensional (2D) and tridimensional (3D) GBM stem cells like (GSC). Our results show that some HDAC inhibitors show antiproliferative properties at 21-32 µM. These results suggest that in this 3D culture, HDACs could be the most relevant targets that are modulated to induce the antiproliferative effects that require in the future further experimental studies.

Mapping the hyperlinks and networks of Central and South American capital cities in three languages: consistencies and variations.

In a globalized, urbanized and knowledge/information world, mapping information about places is critical for a city's local, regional, and international standing. Those networks are important in a city's positioning within a country and in a larger regional and global context. We investigate these linkages and networks by exploring the regional networks of 8 Central and 13 South American capital cities plus São Paulo and Rio de Janeiro. Our research adds a new dimension to urban places by exploring variations in the hyperlink volumes and networks in English as well as Spanish and Portuguese. Sizable language differences but also regularities were evident in the hyperlink volumes of individual cities and in hyperlink pairs. The maps illustrate regional variations and unevenness in the knowledge about places and their networking in a Latin American context.

Diseño de un bipedestador semiautomático reajustable para el desplazamiento de personas con paraplejia / Design of a semi-automatic adjustable standing frame for paraplegics

Introducción: La paraplejia es una condición de salud ocasionada por lesiones lumbares que conlleva a las personas a permanecer la mayor parte de su tiempo postradas, ocasionando problemas de respiración, variaciones en la presión arterial y la aparición de úlceras en sus partes de apoyo. Objetivo: Desarrollar un sistema mecatrónico que permita la bipedestación de personas con condición de paraplejias. Métodos: La investigación se realizó en dos etapas, el desarrollo de un sistema mecatrónico y una fase de validación de uso por usuarios con discapacidad motora. Resultados: Las pruebas de funcionamiento muestran que los atractivos más importantes del equipo son su capacidad de ajuste (permitiendo su uso a personas con diferencias antropométricas) y su operatividad. Conclusiones: El bipedestador diseñado cumplió las condiciones requeridas para realizar la transición a condición bípeda, con las medidas de seguridad en las partes críticas que garantizan la estabilidad del usuario. Además, el bipedestador posee mecanismos sencillos de operar, acorde con sus capacidades. La validación del implemento demostró que es de un tamaño adecuado y de fácil utilización, además al ser reajustable para su uso independientemente de la condición morfométrica.(AU)

Introduction: Paraplegia is an impairment in motor functioning of the lower extremities. Caused by lumbar lesions, it deprives its sufferers from their ability to move about, which results in breathing problems, arterial pressure variations and the appearance of ulcers in pressure areas. Objective: Develop a mechatronic system permitting the bipedal locomotion of paraplegics. Methods: The study was structured into two stages: development of a mechatronic system and validation of its use by people with motor disability. Results: Function tests show that the most attractive features of the device are its adjustability (allowing use by anthropometrically different people) and its operability. Conclusions: The standing frame designed met the conditions required for the transition to bipedal condition, with safety measures in its critical parts which ensure user stability. Additionally, its mechanisms are easy to operate, in keeping with its capabilities. Validation of the device showed that its size is appropriate, its operation simple, and it may be readjusted for use in different morphometric conditions(AU)

Recommendations for airway management in a suspected or confirmed case with COVID-19. A protocol of the Department of Cardiovascular Anesthesia of the National Institute of Cardiology Ignacio Chávez / Recomendaciones para el manejo de la vía aérea en caso sospechoso y/o confirmado con COVID-19. Protocolo del Departamento de Anestesiología Cardiovascular del Instituto Nacional de Cardiología Ignacio Chávez

The new coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), detected in Wuhan, China, causes coronavirus disease 2019 (COVID-19), which was declared pandemic, and has caused more than 19 million confirmed cases and more than 700 thousand deaths worldwide. When our institution was converted to COVID's hospital since early April 2020, specific care protocols were developed, with the aim of improving the quality of care and safety of patients and the staff involved in their management. Airway management represents one of the highest risks of direct contact infection with aerosol generation (orotracheal intubation, secretion aspiration, extubation, cardiopulmonary resuscitation, high flow oxygen therapy, noninvasive ventilation, and invasive ventilation). We present the current recommendations for airway management as well as a step-by-step airway management protocol to carry out a more secure procedure based on the literature reported so far.

El nuevo coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), detectado en Wuhan (China), causante de la enfermedad por coronavirus 2019 (COVID-19), que se declaró como pandemia, ha causado más de 19 millones de casos confirmados y más de 700 mil muertes en el mundo. Nuestra institución se reconvirtió a hospital COVID desde principios de abril del 2020, con lo que se desarrollaron protocolos de atención específicos, con el objetivo de mejorar la calidad de atención y seguridad de los pacientes y el personal involucrado en su manejo. El manejo de la vía aérea representa uno de los riesgos más altos de contagio por contacto directo en la generación de aerosoles (intubación orotraqueal, aspiración de secreciones, extubación, resucitación cardiopulmonar, terapia de oxígeno de alto flujo, ventilación no invasiva y ventilación invasiva). Presentamos las recomendaciones actuales para el manejo de la vía aérea, así como un protocolo de manejo paso a paso para llevar a cabo un procedimiento con mayor seguridad basados en la literatura reportada hasta el momento.

Synthesis and In Vitro Evaluation of Tetrahydroquinoline Derivatives as Antiproliferative Compounds of Breast Cancer via Targeting the GPER.

BACKGROUND: Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells. OBJECTIVE: In an effort to develop new therapeutic strategies against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA. METHODS: This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines. RESULTS: In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and molecular dynamics simulations of the target compounds were performed with GPER to explore their binding mode and free energy values. In addition, the target small molecules were synthesized and assayed in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands reach the GPER-binding site in a similar way, as was demonstrated through in silico studies. CONCLUSION: A concentration-dependent inhibition of cell proliferation occurred with compound 2 in the two cell lines regardless of GPER.

Exploring the conformational and binding properties of unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 through docking and molecular dynamics simulations.

B-cell lymphoma (Bcl-2) is commonly associated with the progression and preservation of cancer and certain lymphomas; therefore, it is considered as a biological target against cancer. Nevertheless, evidence of all its structural binding sites has been hidden because of the lack of a complete Bcl-2 model, given the presence of a flexible loop domain (FLD), which is responsible for its complex behavior. FLD region has been implicated in phosphorylation, homotrimerization, and heterodimerization associated with Bcl-2 antiapoptotic function. In this contribution, homology modeling, molecular dynamics (MD) simulations in the microsecond (µs) time-scale and docking calculations were combined to explore the conformational complexity of unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 systems. Conformational ensembles generated through MD simulations allowed for identifying the most populated unphosphorylated/phosphorylated monomeric conformations, which were used as starting models to obtain trimeric complexes through protein-protein docking calculations, also submitted to µs MD simulations. Principal component analysis showed that FLD represents the main contributor to total Bcl-2 mobility, and is affected by phosphorylation and oligomerization. Subsequently, based on the most representative unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 conformations, docking studies were initiated to identify the ligand binding site of several known Bcl-2 inhibitors to explain their influence in homo-complex formation and phosphorylation. Docking studies showed that the different conformational states experienced by FLD, such as phosphorylation and oligomerization, play an essential role in the ability to make homo and hetero-complexes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 393-413, 2016.

Citrus juice extraction systems: effect on chemical composition and antioxidant activity of clementine juice.

Clementines are especially appreciated for their delicious flavor, and recent years have seen a great increase in the consumption of clementine juice. In previous decades, antioxidant compounds have received particular attention because of widely demonstrated beneficial health effects. In this work, the organoleptic, volatile flavor, and antioxidant quality of clementine juice were studied with regard to the influence on them by different juice extraction systems: plug inside fruit and rotating cylinders. The results showed that juice extracted by the former method presented higher yields and hesperidin content, which was related to higher antioxidant activity, demonstrated by ORAC and LDL assays. The organoleptic quality was not affected by the processing technique, whereas there were significant differences in the chemical flavor profile. There are important differences in chemical and functional quality between juice extraction techniques, which must be taken into account when employing processing systems to produce high-quality products.

Comparison of two immunomagnetic separation technologies to deplete T cells from human blood samples.

The objective of this study was to compare the performance of two immunomagnetic separation technologies to deplete T cells from buffy coats of human blood. Specifically, two versions of the commercial MACS(R) Technology: MiniMACS and SuperMACS, and a prototype, flow-through system, the QMS, were evaluated. Peripheral blood mononuclear leukocytes (PBL) were isolated from buffy coats and an immunomagnetic separation of CD3(+) cells was conducted using company and optimized labeling protocols. To mimic peripheral blood containing bone marrow purged hematopoietic stem cells, HSC, CD34 expressing-cells (KG1a) were spiked into PBL prior to T-cell depletion once optimized depletion conditions were determined. Once the labeling protocol was optimized, the MiniMACS system performed well by producing a highly enriched CD3(+) fraction, and a respectable level of depletion of T cells and recovery of KG1a cells in the depleted fraction; an average log(10) depletion of T cells of 2.88 +/- 0.17 and an average recovery of the KG1a cells of 60.8 +/- 5.94% (n = 14). The performance of the SuperMACS system was very similar with an average log(10) depletion of T cells of 2.89 +/- 0.22 and an average recovery of KG1a of 63.1 +/- 8.55% (n = 10). In contrast, the QMS system produced an average log(10) depletion of T cells of 3.98 +/- 0.33 (n = 16) with a corresponding average recovery of 57.9 +/- 16.6% of the spiked CD34+ cells. The aforementioned QMS performance values were obtained using sorting speeds ranging from 2.5 x 10(4) to 1.7 x 10(5) cells per second. It is suggested that the lack of a 100% recovery of the unlabeled KG1a cells is the result of a previously reported "drafting" phenomena which pulls unlabeled cells in the direction of the magnetically labeled cells thereby resulting in loss of the unlabeled cells.

Cell enrichment and immunochemical staining.

Cell populations can be enriched using a number of physicochemical methods based on characteristics, such as density, size, and volume. Centrifugation using density gradients is typically applied to isolate populations with similar characteristics. Cells obtained using these methods can be further authenticated using specific antibodies that react to markers on the cell surface, allowing the identification of cell subtypes.

Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation.

OBJECTIVE: To develop a reliable technique to enrich for rare cells in blood suspensions using only negative selection steps including a flow-through immunomagnetic cell separations system and by optimizing variables normally encountered during such enrichment processes. METHODS: A human breast cancer cell line was cultivated and spiked at a ratio of 1 cancer cell to 10(5) total leukocytes in buffy coat or 1 cancer cell to 10(8) total cells in whole blood samples. The final, optimized process consisted of: a red cell lysis step, immunomagnetically staining leukocytes with an anti-CD45 PE, anti- MACS sandwich, immunomagnetic sorting using a flow-through system (QMS), and a final cell analysis step using either an automated cell counter, filtration, and visual counting or a cytospin analysis. RESULTS: The final, optimized process produced a final enrichment of the rare cancer cells of 5.17 log(10) and an average, final recovery of 46%. It should be noted that a negative depletion protocol was used (i.e., no labeling of the rare cancer cells was used). CONCLUSIONS: To the authors' knowledge, no examples in the literature exist of a 5.17 log(10) enrichment of cancer cells in human blood using a negative depletion protocol. The closest example is a 4 log(10) enrichment in which two positive magnetic cell separation steps were used (none were used in this study). Ongoing studies are investigating further modifications of the precommercial, prototype flow-through immunmagnetic separation system to increase both the enrichment and recovery rate. However, even at current performance levels, the presented process could significantly improve visual and molecular analysis of rare cells in blood.

Evaluación de consecuencias medioambientales de accidentes severos gaves (Seveso II)

La Directiva Seveso II desarrolla las políticas encaminadas a la prevención de accidentes graves en actividades industriales con sustancias peligrosas y a la reducción de sus consecuencias para las personas, los bienes y el medio ambiente. En este ultimo ámbito, los requisitos derivados de la aplicación de la misma en materia de análisis de las consecuencias encuentran limitaciones por causa de la complejidad de los procesos de transporte y mecanismos de afectación del medio ambiente en el articulo se esboza el desarrollo de una metodología que, aplicando la norma UNE 150 008 EX persigue la objetivación de los parámetros contemplados en la misma - cantidad de sustancia, peligrosidad, extensión y calidad del medio - considerando las diferentes naturalezas del transporte y la afección en diferentes ámbitos que componen el medio natural (suelo, atmósfera y aguas). (AU)

Quiste óseo aneurismático / Aneurysmal bone cyst

Paciente de 3 meses de edad, es internado por hematemesis y bronquitis obstructiva. La radiografía de Tórax y T.A.C. de pulmón muestran la imagen de un tumor sólido en pulmón derecho. El tumor es extirpado y el diagnóstico anatomapatológico es Quiste óseo aneurimático de costilla. El objetivo de esta presentación es la forma atípica de presentación de este tumor.