Informe Optoel 2021

[No abstract available

In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo

Indexación: Scopus.Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2018.00209/ful

Nanoscopic mechanical anisotropy in hydrogel surfaces

The bulk mechanical properties of soft materials have been studied widely, but it is unclear to what extent macroscopic behavior is reflected in nanomechanics. Using an atomic force microscopy (AFM) imaging method called force spectroscopy mapping (FSM), it is possible to map the nanoscopic spatial distribution of Young's modulus, i.e. “stiffness,” and determine if soft or stiff polymer domains exist to correlate nano- and macro-mechanics. Two model hydrogel systems typically used in cell culture and polymerized by a free radical polymerization process, i.e. poly (vinyl pyrrolidone) (PVP) and poly(acrylamide) (PAam) hydrogels, were found to have significantly different nanomechanical behavior despite relatively similar bulk stiffness and roughness. PVP gels contained a large number of soft and stiff nanodomains, and their size was inversely related to crosslinking density and changes in crosslinking efficiency within the hydrogel. In contrast, PAam gels displayed small nanodomains occuring at low frequency, indicating relatively uniform polymerization. Given the responsiveness of cells to changes in gel stiffness, inhomogeneities found in the PVP network indicate that careful nanomechanical characterization of polymer substrates is necessary to appreciate complex cell behavior

Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma

PURPOSE: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). PATIENTS AND METHODS: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1, 100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. RESULTS: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%. CONCLUSION: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM

The Mexican consensus on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy

Más de 30 millones de personas consumen diariamente antiinflamatorios noesteroideos (AINE) en el mundo, y este consumo se ve incrementado anualmente. Aunque losAINE poseen propiedades analgésicas y antiinflamatorias, sus eventos adversos gastrointesti-nales son bien reconocidos. En nuestro país no existía un consenso respecto al diagnóstico,tratamiento y prevención de la gastropatía y la enteropatía por AINE, por lo que la AsociaciónMexicana de Gastroenterología reunió a un grupo de expertos para establecer recomendacionesde utilidad para la comunidad médica. En este consenso se emitieron 33 recomendaciones. Elconsenso destaca que el riesgo de toxicidad gastrointestinal de los AINE varía según el fármacoempleado y su farmacocinética, lo cual debe ser considerado al momento de su prescripción. Losfactores de riesgo de complicación gastroduodenal por AINE son: antecedente de úlcera pép-tica, edad mayor a 65 a˜nos, dosis altas del AINE, infección por Helicobacter pylori (H.pylori), ypresencia de comorbilidades graves. Los síntomas y el da˜no gastroduodenal inducido por AINEson variables ya que puede cursar asintomático o manifestarse como anemia por deficiencia dehierro, hemorragia, estenosis y perforación. La cápsula endoscópica y la enteroscopia son méto-dos diagnósticos directos en la enteropatía por AINE. Respecto a la prevención, se recomiendaprescribir la dosis mínima necesaria de un AINE para obtener el efecto deseado y durante elmenor tiempo. Finalmente, los inhibidores de la bomba de protones (IBP) representan el están-dar de oro para la profilaxis y tratamiento de los efectos gastroduodenales, mas no son útilesen la enteropatía

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio