Adaptación de la Metodología Analítica para la determinación de residuos de plaguicidas en frutas nativas de exportación mediante Uplc-Ms/Ms

Se investigó el potencial analítico y la aplicabilidad del acoplamiento instrumental en cromatografía líquida de ultra eficiencia-espectrometría de masas en tándem con analizador de doble cuadrupolo (UPLC-MS/MS), para el desarrollo, optimización y adaptación para determinación de pesticidas carbámicos y organofosforados en muestras de frutas como camu-camu, chirimoya y lúcuma que poseen interés de exportación. Para ello, se han seleccionado compuestos cuya determinación analítica presentan dificultades, bien por su elevada polaridad o por problemas en su ionización, así como contaminantes prioritarios desde el punto de vista medioambiental. Toda la metodología y su optimización analítica incluida en el trabajo de investigación se ha desarrollado teniendo en cuenta la legislación europea y americana vigentes, tanto en lo relativo a la sensibilidad requerida en los métodos analíticos según los niveles máximos de residuos permitidos, como a los parámetros de calidad relacionados con la instrumentación analítica y los métodos empleados. En consecuencia, los resultados que se presentan pueden ser considerados satisfactorios y fiables, desde el punto de vista cuantitativo y cualitativo, lo que sería un aporte a la normatividad de nuestro país. La excelente sensibilidad y selectividad alcanzadas, así como la rapidez y robustez de los métodos desarrollados y optimizados hace factible su aplicación en análisis rutinarios de muestras. En cuanto a la metodología multirresidual, para carbámicos y organofosforados en el presente trabajo se propone una aproximación, basada en una preconcentración SPE “ extracción en fase sólida ” previa a la determinación por UPLC-MS/MS, para la determinación de pesticidas carbámicos ( Aldicarb, Carbofurano, Carbaryl, Metomilo y Propoxur ) y organofosforados (Malatión, Paratión y Metamidofos), ampliamente usados en nuestro país. La inyección directa de la muestra en presencia de ácido fórmico en la fase móvil y la aplicación del sistema de preconcentración SPE, previa extracción por el procedimiento de extracción en matrices complejas , lo que permite la retención satisfactoria de compuestos básicos o ácidos, respectivamente, consiguiendo de este modo un elevado grado de multirresidualidad. Mediante la adquisición de dos transiciones SRM por compuesto se puede cuantificar y confirmar diversos pesticidas, mayoritariamente polares y algunos medianamente polares, al nivel del límite de cuantificación (LOQ) objetivo (0.025 μg/L). Además, la elevada sensibilidad de los métodos desarrollados da lugar a límites de detección (LOD) inferiores a 0.005 μg/L en la mayoría de los casos. El desarrollo y la optimización se llevó a cabo a dos niveles de fortificación para pesticidas carbámicos y organofosforados (5 y 40 μg/L), obteniendo recuperaciones entre 70 y 110%. Palabras clave: UPLC-MS/MS, Pesticidas carbámicos y Organofosforados, QuEChERS, SPE, Adaptación, desarrollo y optimización de la metodología analitica.-- In this work we investigate the analytical potential and applicability of the coupling instrumental in efficiency ultra performance liquid chromatography-mass spectrometry in tandem with double quadrupole analyzer (UPLC-MS/MS) for the development, optimization and adaptation for the determination of pesticides, carbamates and organophosphates in fruit samples as camu-camu, chirimoya and lucuma that have export interest. We selected compounds that present difficulties in their analytical determination either for their high polarity or problems in their ionization and priority pollutants from the environmental viewpoint. All analytical optimization methodology and included in the work has been developed taking into account European law, both in American force on the sensitivity required in analytical methods based on maximum residue levels allowed, as quality parameters related with analytical instrumentation and methods. Consequently, the results presented can be considered satisfactory and reliable, from a quantitative and qualitative contributing to its regulations in our country. The excellent sensitivity and selectivity achieved, and the speed and robustness of the methods developed and optimized makes possible its application in routine analysis of samples. In terms of methodology multirresidual to carbamates and organophosphates in the work proposes an approach based on a preconcentration SPE "solid phase extraction" predetermination UPLC-MS/MS for the determination of carbamate pesticides (Aldicarb, Carbofuran, Carbaryl, Methomyl and Propoxur) and organophosphates (malathion, parathion and methamidophos) widely used in our country. Direct injection of the sample in the presence of formic acid in mobile phase and the implementation of the SPE preconcentration system after extraction by the extraction procedure in complex matrices with a robust, fast, easy, cheap, effective and safe ( QuEChERS), allowing satisfactory retention of basic compounds or acids, respectively, thereby achieving a high degree of multirresidualidad. Through the acquisition of two SRM transitions per compound can be quantified and confirm various pesticides, mostly moderately polar and some polar, the level of the limit of quantitation (LOQ) objective (0.025 mg / L). Furthermore, the high sensitivity of the methods developed resulting in limits of detection (LOD) of less than 0,005 ug / L in most cases. The development and optimization was carried out at two levels of fortification for carbamate and organophosphate pesticides (25 and 10 ug / L), obtaining recoveries between 70 and 110%. -- Keywords: UPLC-MS/MS, carbamate and organophosphate pesticides, QuEChERS, SPE, Adaptation, Development and Optimization of Analytical Methodology.Tesi

RESISTENCIA A LA INSULINA Y SU CORRELACIÓN CON INTERLEUCINA-6 (IL-6) EN NIÑOS Y ADOLESCENTES DE SAN LUIS POTOSÍ (MEXICO)

La resistencia a la insulina parece ser consecuencia de un estado de inflamación sistémica de bajo grado presente en la obesidad y en diabetes tipo 2. Actualmente se ha observado un incremento de obesidad y diabetes tipo 2 en población infantil y adolescente. El objetivo es conocer si existe asociación de resistencia a la insulina con niveles de IL-6 en población infantil seleccionada de manera aleatoria. Se incluyeron 184 niños (100 niñas) entre 6-12 años de edad, elegidos al azar de Escuelas de Educación Pública de la Ciudad de San Luís Potosí, México. Se evaluaron las medidas antropométricas: edad, peso, talla, IMC e ICC. Se tomaron muestras de sangre venosa, previo ayuno de 12 horas, para las determinaciones de glucosa, colesterol total, triglicéridos, lipoproteínas de alta y baja densidad (HDL-C) y (LDL-C). Las concentraciones de insulina se evaluaron por radioinmunoanálisis, se calculó el índice de resistencia a la insulina por el modelo homeostático HOMA-IR. Las concentraciones de IL-6 se realizaron por quimioluminiscencia. Los valores de IL-6 se encuentran asociados con los niveles de insulina (r = 0.144, p<0.051), colesterol (r = 0.145, p<0.052), IMC (r = 0.170, p<0.021), HDL-C (r = -0.180, p<0.01) y el HOMA-IR (r = 0.142, p<0.055). La cuantificación de IL-6 enniños es útil para conocer desde edades tempranas el grado de inflamación asociado a la resistencia a la insulina en población mexicana.Palabras clave: niños, obesidad, inflamación, interleucina 6obesity, children, inflammation, interleukin 6

Fermentation of Vaccinium floribundum Berries with Lactiplantibacillus plantarum Reduces Oxidative Stress in Endothelial Cells and Modulates Macrophages Function

Accumulating evidence suggests that high consumption of natural antioxidants promotes health by reducing oxidative stress and, thus, the risk of developing cardiovascular diseases. Similarly, fermentation of natural compounds with lactic acid bacteria (LAB), such as Lactiplantibacillus plantarum, enhances their beneficial properties as regulators of the immune, digestive, and cardiovascular system. We investigated the effects of fermentation with Lactiplantibacillus plantarum on the antioxidant and immunomodulatory effects of Pushgay berries (Vaccinium floribundum, Ericaceae family) in human umbilical vein endothelial cells (HUVECs) and macrophage cell line RAW264.7. Polyphenol content was assayed by Folin-Ciocalteu and HPLC-MS/MS analysis. The effects of berries solutions on cell viability or proliferation were assessed by WST8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and Lactate dehydrogenase (LDH) release, Trypan blue exclusion test, and Alamar blue assay. Antioxidant activity was evaluated by a cell-based chemiluminescent probe for the detection of intracellular H2O2 production in HUVECs. Heme oxygenase-1 (HO-1) expression levels were investigated by RT-qPCR. Glutathione reductase (GR), glutathione peroxidase (Gpx), superoxide dismutase (SOD), and catalase (CAT) activities, as markers of intracellular antioxidant defense, were evaluated by spectrophotometric analysis. The immunomodulatory activity was examined in RAW 264.7 by quantification of inducible nitric oxide synthase (iNOS) and Tumor Necrosis Factor-alpha (TNF alpha) by RT-qPCR. Data showed that fermentation of Pushgay berries (i) enhances the content of quercetin aglycone, and (ii) increases their intracellular antioxidant activity, as indicated by the reduction in H2O2-induced cell death and the decrease in H2O2-induced HO-1 gene expression in HUVECs treated for 24 h with fermented berries solution (10 mu g/mL). Moreover, treatment with Pushgay berries for 72 h (10 mu g/mL) promotes cells growth in RAW 264.7, and only fermented Pushgay berries increase the expression of iNOS in the same cell line. Taken together, our results show that LAB fermentation of Pushgay berries enhances their antioxidant and immunomodulatory properties

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Performance of the CMS muon trigger system in proton-proton collisions at √s = 13 TeV

The muon trigger system of the CMS experiment uses a combination of hardware and software to identify events containing a muon. During Run 2 (covering 2015-2018) the LHC achieved instantaneous luminosities as high as 2 × 10 cm s while delivering proton-proton collisions at √s = 13 TeV. The challenge for the trigger system of the CMS experiment is to reduce the registered event rate from about 40 MHz to about 1 kHz. Significant improvements important for the success of the CMS physics program have been made to the muon trigger system via improved muon reconstruction and identification algorithms since the end of Run 1 and throughout the Run 2 data-taking period. The new algorithms maintain the acceptance of the muon triggers at the same or even lower rate throughout the data-taking period despite the increasing number of additional proton-proton interactions in each LHC bunch crossing. In this paper, the algorithms used in 2015 and 2016 and their improvements throughout 2017 and 2018 are described. Measurements of the CMS muon trigger performance for this data-taking period are presented, including efficiencies, transverse momentum resolution, trigger rates, and the purity of the selected muon sample. This paper focuses on the single- and double-muon triggers with the lowest sustainable transverse momentum thresholds used by CMS. The efficiency is measured in a transverse momentum range from 8 to several hundred GeV

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Search for long-lived particles decaying to jets with displaced vertices in proton-proton collisions at root s=13 Te V

A search is presented for long-lived particles produced in pairs in proton-proton collisions at the LHC operating at a center-of-mass energy of 13 TeV. The data were collected with the CMS detector during the period from 2015 through 2018, and correspond to a total integrated luminosity of 140 fb(-1). This search targets pairs of long-lived particles with mean proper decay lengths between 0.1 and 100 mm, each of which decays into at least two quarks that hadronize to jets, resulting in a final state with two displaced vertices. No significant excess of events with two displaced vertices is observed. In the context of R-parity violating supersymmetry models, the pair production of long-lived neutralinos, gluinos, and top squarks is excluded at 95% confidence level for cross sections larger than 0.08 fb, masses between 800 and 3000 GeV, and mean proper decay lengths between 1 and 25 mm.Peer reviewe