Translocated LPS Might Cause Endotoxin Tolerance in Circulating Monocytes of Cystic Fibrosis Patients

Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes

Zoología. Un modelo para la enseñanza no presencial

Memoria Proyecto de innovación nº 238 curso 2020/2

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Actas de las V Jornadas ScienCity 2022. Fomento de la Cultura Científica, Tecnológica y de Innovación en Ciudades Inteligentes

ScienCity es una actividad que viene siendo continuada desde 2018 con el objetivo de dar a conocer los conocimientos y tecnologías emergentes siendo investigados en las universidades, informar de experiencias, servicios e iniciativas puestas ya en marcha por instituciones y empresas, llegar hasta decisores políticos que podrían crear sinergias, incentivar la creación de ideas y posibilidades de desarrollo conjuntas, implicar y provocar la participación ciudadana, así como gestar una red internacional multidisciplinar de investigadores que garantice la continuación de futuras ediciones. En 2022 se recibieron un total de 48 trabajos repartidos en 25 ponencias y 24 pósteres pertenecientes a 98 autores de 14 instituciones distintas de España, Portugal, Polonia y Países Bajos.Fundación Española para la Ciencia y la Tecnología-Ministerio de Ciencia, Innovación y Universidades; Consejería de la Presidencia, Administración Pública e Interior de la Junta de Andalucía; Estrategia de Política de Investigación y Transferencia de la Universidad de Huelva; Cátedra de Innovación Social de Aguas de Huelva; Cátedra de la Provincia; Grupo de investigación TEP-192 de Control y Robótica; Centro de Investigación en Tecnología, Energía y Sostenibilidad (CITES

Neutral Hexacoordinate Tin(IV) Halide Complexes with 4,4'‐Dimethy‐2,2'‐bipyridine

A series of three neutral, hexacoordinate tin(IV) complexes were synthesized by the reaction of 4,4'‐dimethyl‐2,2'‐bipyridine (DMB) with SnX4, X = Cl, Br, and I, as starting materials. The complexes (DMB)SnX4 were characterized in solution by 1H, 13C, and 119Sn NMR spectroscopy, and in the solid‐state by 119Sn MAS NMR spectroscopy. In addition, single‐crystal X‐ray diffraction and elemental analysis were used to confirm the molecular structures. In these complexes, the tin atom adopts a distorted octahedral arrangement and the DMB acts as a bidentate N,N'‐chelate ligand. Computational DFT methods were also employed to gain more insight into the nature of the bonding in these complexes, including the hypothetical complexes (DMB)SnX4 (X = F, At). Additionally, the validity and reliability of the 119Sn NMR chemical shifts were examined. The calculated values were compared with the experimental signals and the effects of structure and solvent are discussed. Finally, all of the complexes (DMB)SnX4 were successfully tested for the ring‐opening polymerization (ROP) of bulk ε‐caprolactone under non‐dried and aerobic conditions as precatalyst

Comprehensive characterization of neurochemicals in three zebrafish chemical models of human acute organophosphorus poisoning using liquid chromatography-tandem mass spectrometry

There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of development. Zebrafish, a vertebrate model increasingly used in neurobiology and neurotoxicology, shares the common neurotransmitter systems with mammals, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin, acetylcholine, and histamine. In this study, we have evaluated the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the multiresidue determination of neurotransmitters and related metabolites. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined to optimize two selected reaction monitoring (SRM) transitions. Chromatographic conditions were optimized considering the chemical structure and chromatographic behavior of the analyzed compounds. The best performance was obtained with a Synergy Polar-RP column, which allowed the separation of the 38 compounds in 30 min. In addition, the performance of LC-MS/MS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method was able to quantify 27 of these neurochemicals in zebrafish chemical models for mild (P1), moderate (P2), and severe (P3) acute organophosphorus poisoning (OPP). The results show a general depression of synaptic-related neurochemicals, including the excitatory and inhibitory amino acids, as well as altered phospholipid metabolism, with specific neurochemical profiles associated to the different grades of severity. These results confirmed that the developed analytical method is a new tool for neurotoxicology research using the zebrafish model. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.The research leading to these results has received funding from the European Research Council under European Union's Seven Framework Programme (FP/2007e2013)/ERC Grant Agreement n.320737, the NATO SfP project MD.SFPP 984777, and the grant CTM 2014-51985 from the Spanish Ministry of Economy, Industry and Competitiveness. Moreover, Rita Bausano is acknowledged for extraction samples support during her Erasmus Traineeship stage in the Environmental Chemistry Department at IDEA-CSIC (Barcelona, Spain).Peer reviewe

Modulation of Cytokine Release and Gene Expression by the Immunosuppressive Domain of gp41 of HIV-1

<div><p>The transmembrane envelope protein gp41 of the human immunodeficiency virus HIV-1 plays an important role during infection allowing fusion of the viral and cellular membrane. In addition, there is increasing evidence that gp41 may contribute to the immunodeficiency induced by HIV-1. Recombinant gp41 and a synthetic peptide corresponding to a highly conserved domain in gp41, the immunosuppressive (isu) domain, have been shown to inhibit mitogen-induced activation of human peripheral blood mononuclear cells (PBMCs) and to increase release of IL-6 and IL-10 from these cells. We recently reported that a single mutation in the isu domain of gp41 abrogated the immunosuppressive properties and that HIV-1 sequences containing such abrogating mutations had never been isolated from infected individuals. Here, we studied the influence of the isu peptide on the release of 66 cytokines and the expression of 27,000 genes in PBMCs. Incubation of PBMCs with isu peptide homopolymers increased the expression of 16 cytokines among them IL-6 and IL-10, and decreased that of IL-2 and CXCL9. Interestingly, the extend of cytokine modulation was donor-dependent. Among the genes up-regulated were IL-6, IL-8, IL-10 but also MMP-1, TREM-1 and IL-1beta. Most importantly, genes involved in innate immunity such as FCN1 and SEPP1 were found down-regulated. Many changes in cytokine expression demonstrated in our experiments were also found in HIV-1 infected individuals. These data indicate that the isu domain of gp41 has a broad impact on gene expression and cytokine release and therefore may be involved in HIV-1 induced immunopathogenesis.</p> </div