Preparation and Study of the Antibacterial Applications and Oxidative Stress Induction of Copper Maleamate-Functionalized Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSNs) are an interesting class of nanomaterials with potential applications in different therapeutic areas and that have been extensively used as drug carriers in different fields of medicine. The present work is focused on the synthesis of MSNs containing a maleamato ligand (MSN-maleamic) and the subsequent coordination of copper(II) ions (MSN-maleamic-Cu) for the exploration of their potential application as antibacterial agents. The Cu-containing nanomaterials have been characterized by different techniques and the preliminary antibacterial effect of the supported maleamato-copper(II) complexes has been tested against two types of bacteria (Gram positive and Gram negative) in different assays to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The biological results showed a moderate antibacterial activity against Escherichia coli which motivated a more detailed study of the antibacterial mechanism of action of the synthesized maleamate-containing nanosystems and whose findings showed oxidative stress generation in bacterial cells. All the prepared nanomaterials were also tested as catalysts in the “solvent free” selective oxidation of benzyl alcohol, to observe if there is a potential correlation between the catalytic oxidation capacity of the materials and the observed oxidative stress in bacteria. This may help in the future, for a more accurate rational design of antibacterial nanosystems, based on their observed catalytic oxidation activity.This research was funded by Ministerio de Ciencia, Innovación y Universidades Spain-FEDER, grants number CTQ2015-66164-R and CTQ2017-90802-REDT and by Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (PICT 2015 Nº1558)

Implementación de herramientas para el diseño de sistemas de gestión de la calidad: Aproximación metodológica en un caso aplicado al sector de la construcción

Quality management systems (QMS) are management tools based on ISO 9001:2015 international standard that are of great importance for organizations in any economic sector of society, who wish to impact customer satisfaction, their competitiveness in today's global markets and the establishment of quality standards for their products and services. This article presents the design of the QMS based on the application of a methodology proposed for the case of a company in the construction sector; this methodology is understood as the integration of different management tools in the process of designing the system with a focus on compliance with the requirements of NTC-ISO 9001:2015. The design starts with the analysis of the maturity level of the company to know the organizational situation, according to the requirements of the standard, then the requirements related to the knowledge of the context of the organization, the strategic approach of the QMS, the organization by processes and the identification and evaluation of risks and opportunities associated with the context are defined. Knowledge of the current state of the organization and its context is obtained, the management system is established as a strategic direction tool for the company, the processes are satisfactorily characterized, according to the scope of the QMS and the intentions of the top management, preventive measures related to the achievement of the objectives of the human management process are defined, as well as the objectives of the QMS. It is concluded that the design of the QMS integrating tools such as the evaluation of maturity levels, the Supersystems Map, the Balanced Scorecard, BSC, the definition of S.M.A.R.T. objectives, risk management and Xertatu:adi methodology, allow to objectively evaluate the compliance with the requirements of the NTC-ISO 9001:2015 and establish the management system as a strategic management tool for the company.Los sistemas de gestión de la calidad (SGC) son herramientas de gestión basados en el estándar internacional ISO 9001:2015 que son de gran importancia para las organizaciones de cualquier sector económico de la sociedad, que deseen impactar en la satisfacción de sus clientes, en su competitividad ante los mercados globales actuales y en el establecimiento de estándares de calidad para sus productos y servicios. En este artículo se expone el diseño del SGC a partir de la aplicación de una metodología propuesta para el caso de una empresa del sector de la construcción; entendida esta metodología como la integración de diferentes herramientas de gestión en el proceso de diseño del sistema con enfoque en el cumplimiento a los requisitos de la NTC-ISO 9001:2015. El diseño parte del análisis del nivel de madurez de la empresa para conocer la situación organizacional, según requerimientos de la norma, luego se definen los requisitos relacionados con el conocimiento del contexto de la organización, el planteamiento estratégico del SGC, la organización por procesos y la identificación y evaluación de los riesgos y las oportunidades asociadas al contexto. Se obtiene un conocimiento del estado actual de la organización y se aumenta el conocimiento sobre su contexto, se  establece el sistema de gestión como herramienta de direccionamiento estratégico para la empresa, se caracterizan los procesos de forma satisfactoria, según el alcance del SGC y las intenciones de la alta dirección, se definen las medidas preventivas relacionadas con el logro de los objetivos del proceso de gestión humana, así como los objetivos del SGC. Se concluye que el diseño del SGC integrando herramientas como la evaluación de niveles de madurez, el Mapa de Supersistemas, el Balanced Scorecard, BSC, la definición de objetivos S.M.A.R.T. la administración del riesgo y metodología Xertatu:adi, permiten evaluar de maneja objetiva el cumplimiento de requisitos de la NTC-ISO 9001:2015 y establecer el sistema de gestión como herramienta de direccionamiento estratégico para la empresa

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation

Background This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. Methods CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI. Results A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1–53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL. Conclusions More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery

Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients

Background: About 40% of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR-based therapy have poor outcomes. Treatment failure is not only associated with poorer prognosis but higher healthcare costs. Our aim was to identify novel somatic genetic variants in the primary tumor and assess their effect on anti-EGFR response. Patients and Methods: Tumor (somatic) and blood (germline) DNA samples were obtained from two well-defined cohorts of mCRC patients, those sensitive and those resistant to EGFR blockade. Genetic variant screening of 43 EGFR-related genes was performed using targeted next-generation sequencing (NGS). Relevant clinical data were collected through chart review to assess genetic results. Results: Among 61 patients, 38 were sensitive and 23 were resistant to treatment. We identified eight somatic variants that predicted non-response. Three were located in insulin-related genes (I668N and E1218K in IGF1R, T1156M in IRS2) and three in genes belonging to the LRIG family (T152T in LRIG1, S697L in LRIG2 and V812M in LRIG3). The remaining two variants were found in NRAS (G115Efs*46) and PDGFRA (T301T). We did not identify any somatic variants related to good response. Conclusions: This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and LRIG genes on anti-EGFR efficacy. Our findings could help characterize patients who are resistant to anti-EGFR blockade despite harboring RAS/BRAF wild-type tumors

The K2-ESPRINT Project. I. Discovery of the Disintegrating Rocky Planet K2-22b with a Cometary Head and Leading Tail

We present the discovery of a transiting exoplanet candidate in the K2 Field-1 with an orbital period of 9.1457 hr: K2-22b. The highly variable transit depths, ranging from $\sim$0\% to 1.3\%, are suggestive of a planet that is disintegrating via the emission of dusty effluents. We characterize the host star as an M-dwarf with $T_{\rm eff} \simeq 3800$ K. We have obtained ground-based transit measurements with several 1-m class telescopes and with the GTC. These observations (1) improve the transit ephemeris; (2) confirm the variable nature of the transit depths; (3) indicate variations in the transit shapes; and (4) demonstrate clearly that at least on one occasion the transit depths were significantly wavelength dependent. The latter three effects tend to indicate extinction of starlight by dust rather than by any combination of solid bodies. The K2 observations yield a folded light curve with lower time resolution but with substantially better statistical precision compared with the ground-based observations. We detect a significant "bump" just after the transit egress, and a less significant bump just prior to transit ingress. We interpret these bumps in the context of a planet that is not only likely streaming a dust tail behind it, but also has a more prominent leading dust trail that precedes it. This effect is modeled in terms of dust grains that can escape to beyond the planet's Hill sphere and effectively undergo `Roche lobe overflow,' even though the planet's surface is likely underfilling its Roche lobe by a factor of 2.Comment: 22 pages, 16 figures. Final version accepted to Ap

Consensus of experts from the Spanish pharmacogenetics and pharmacogenomics society and the Spanish society of medical oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidinesThis project has been financed with SEOM and SEFF resource

Prospección acústico-pesquera y caracterización ambiental de algunos recursos de tipo demersal en el Caribe colombiano

Within the framework of the fishing program Vecep (Inpa-Colombia) a pilot acoustic survey was carried out for the reconnaissance of bottoms and demersal resources, previous to the evaluation by the swept area method made by the same program. The survey was made in the strip between the outer limit of the artisanal fishing zone and the external edge of the continental shelf, and from Punta Gallinas to Cabo Tiburón, on the Colombian Caribbean.&nbsp; Some fishing operations with bottom long lines also took place, as well as oceanographic stations in all the wurveyed area.&nbsp; Although some resultos of interest were disclosed to the businessmen in the fishing sector through a technical bulletin and a workshop, the main results had not yet been formally published.&nbsp; The present work rescues the most important aspects from the fishing and oceanographic point of view, making emphasis on the environmental conditions in the sites where groupers and snappers were caught.En el marco del programa de pesca Vecep (Inpa-Colombia) se llevó a cabo una campaña piloto de reconocimiento acustico de los fondos y de recursos demersales, previa a la evaluación por área barrida realizada por ese mismo programa. &nbsp;La campaña se realizó en la franja del Caribe Colombiano comprendida entre el límite exterior de la pesca artesanal y al borde extremo de la plataforma &nbsp;continental y desde Punta Gallinas &nbsp;hasta Cabo Tiburón. &nbsp;Se efectuaron tambien algunas pescas comprobatorias con palangres de fondo, así como estaciones oceanográficas en todo el area prospectada. Aunque algunos resultados de interés fueron divulgados a los industriales del sector pesquero a través de un boletín tecnico y de un taller, los principales resultados no habían sido formalmente publicados. &nbsp;el presente trabajo rescata los aspectos mas relevantes desde el punto de vista pesquero y oceanográfico, haciendo énfasis en las condiciones ambientales de los calderos en que se capturaron pargos y meros de profundida

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation

Background: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. Methods: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-? [IFN-?] ? 0.2 IU/mL) indicated a positive CMV-CMI. Results: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-? level (>12 IU/mL vs ?12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-? level ?12 IU/mL. Conclusions: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-? level, but not the ATG dose, shows a strong association with the kinetics of this recovery.This work was supported by the Fundación Progreso y Salud, Consejería de Salud y Familias, Junta de Andalucía (grant number PI-0294-2014); Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (grant number CP 18/00073 to M. F. R.); Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia e Innovación, Spanish Network for Research in Infectious Diseases (grant numbers REIPI RD16/0016/0002, RD16/0016/0003, RD16/0016/0007, RD16/0016/0008, RD16/0016/0009 and RD16/0016/0012); cofinanced by European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014- 2020; Spanish Network for Research in Renal Diseases (grant numbers RD16/0009/0006, RD16/0009/0008, RD16/0009/0013, RD16/0009/0014, RD16/0009/0019, RD16/0009/0034); Centro de Investigación Biomédica en Red Enfermedades Respiratorias (grant number CB06/06/0058); and Spanish Group for the Study of Infection in Transplantation and the Immunocompromised Host of the Spanish Society of Infectious Diseases and Clinical Microbiolog

Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas

<p>Abstract</p> <p>Background</p> <p>Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed.</p> <p>Methods</p> <p>sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC.</p> <p>Results</p> <p>At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5-81.0%).</p> <p>Conclusions</p> <p>Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary.</p