Polymeric films based on blends of 6FDA-6FpDA polyimide plus several copolyfluorenes for CO2 separation

Producción CientíficaThree emitting copolyfluorenes, based on 2,7-(9,9-dihexyl)fluorene and different aryl groups (1,4-bencene, PFH-B; 1,4-bencen-1,2,5-thiadiazole PFH-BT; 1,4-naphthalen- 1,2,5-thiadiazole, PFH-NT), showing diverse acceptor character, in different proportions were blended with a polyimide 6FDA-6FpDA to make a series of films. These copolyfluorene-polyimide blends were prepared and characterized in solid state, using several techniques. The fluorescence of conjugated polymers can be used as a tool to understand the formation of the membrane and also to increase permeability and selectivity in comparison to films without fluorescence. The relationship between the intrinsic fluorescence of conjugated polyfluorenes and their gas separation properties has been explored in order to establish the influence of the composition and the nature of the aryl group, in the conjugated polymer, on the gas separation performances. In all cases, a low proportion of copolyfluorenes (< 1%weight) gives better CO2/CH4 permselectivity properties than the original pure polyimide matrix. The best results were found for the samples that contain PFH-NT. This sample gives 25 % increase in the CO2 permeability with 15 % increase in CO2/CH4 selectivity. Finally, the loss of efficiency in conjugation mechanisms of absorption and emission of the samples could be explained on the basis of the π-staking of the polymer chains produced when a certain low percentage of conjugated polymers in the blend is surpassed. When this π- staking starts, gas permeation properties start to decline too.Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA302U13

Quantitative Nanomechanical Properties of Multilayer Films Made of Polysaccharides through Spray Assisted Layer-by-Layer Assembly.

Nanomechanical properties of alginate/chitosan (Alg/Chi) multilayer films, obtained through spray assisted layer-by-layer assembly, were studied by means of PeakForce quantitative nanomechanical mapping atomic force microscopy (PF-QNM AFM). Prepared at two different alginate concentrations (1.0 and 2.5 mg/mL) and a fixed chitosan concentration (1.0 mg/mL), Alg/Chi films have an exponential growth in thickness with a transition to a linear growth toward a plateau by increasing the number of deposited bilayers. Height, elastic modulus, deformation, and adhesion maps were simultaneously recorded depending on the number of deposited bilayers. The elastic modulus of Alg/Chi films was found to be related to the mechanism of growth in contrast to the adhesion and deformation. A comparison of the nanomechanical properties obtained for non-cross-linked and thermally cross-linked Alg/Chi films revealed an increase of the elastic modulus after cross-linking regardless alginate concentration. The incorporation of iron oxide nanoparticles (NPs), during the spray preparation of the films, gave rise to nanocomposite Alg/Chi films with increased elastic moduli with the number of incorporated NPs layers. Deformation maps of the films strongly suggested the presence of empty spaces associated with the method of preparation. Finally, adhesion measurements point out to a significant role of NPs on the increase of the adhesion values found for nanocomposite films.journal article2017 01 092016 12 15importe

Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntington's disease models

Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. Yet, it remains unclear how the HTT mutation affects NMDAR function, and direct evidence for a causative role is missing. Here we show that mutant HTT redirects an intracellular store of juvenile NMDARs containing GluN3A subunits to the surface of striatal neurons by sequestering and disrupting the subcellular localization of the endocytic adaptor PACSIN1, which is specific for GluN3A. Overexpressing GluN3A in wild-type mouse striatum mimicked the synapse loss observed in Huntington's disease mouse models, whereas genetic deletion of GluN3A prevented synapse degeneration, ameliorated motor and cognitive decline and reduced striatal atrophy and neuronal loss in the YAC128 Huntington's disease mouse model. Furthermore, GluN3A deletion corrected the abnormally enhanced NMDAR currents, which have been linked to cell death in Huntington's disease and other neurodegenerative conditions. Our findings reveal an early pathogenic role of GluN3A dysregulation in Huntington's disease and suggest that therapies targeting GluN3A or pathogenic HTT-PACSIN1 interactions might prevent or delay disease progression

Frecuencia y factores de riesgo asociados a sobrepeso y obesidad en universitarios de colima, méxico

Objetivo Determinar la frecuencia y factores de riesgo para sobrepeso y obesidad en jóvenes universitarios. Métodos Se realizó un estudio transversal analítico en 821 alumnos inscritos de la Universidad de Colima. Entre las variables analizadas se encuentran: edad, género, alcoholismo, tabaquismo y utilización de medicamentos o sustancias para control de peso. Resultados Se estudiaron 821 alumnos (380 hombres y 441 mujeres) con una edad promedio de 20,9±2,5 años. Las frecuencias de sobrepeso y obesidad en hombres fueron de 27,8 %  y  14,7 % y en mujeres de 17 % y 5,2 %. En hombres el tabaquismo (OR 2,1, IC 95% 1,4-3,8;p=0,01) y etilismo (OR 2,1, IC 95% 1,2-3,6;p=0,003), estuvieron asociados a sobrepeso y obesidad. Fueron factores protectores en ambos géneros el uso de sustancias para control de peso (OR 0,4, IC 95% 0,2-0,8;p=0,01); mientras que el control dietético fue un factor protector sólo en las mujeres (OR 2,2, IC 95% 1,1-3,4;p=0,01). Conclusiones En estudiantes universitarios, el 31,6 % presentó sobrepeso y obesidad. En hombres, el tabaquismo y etilismo se asociaron a sobrepeso y obesidad. El uso de sustancias para bajar de peso y control dietético fueron factores protectores

Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer

Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53) in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV) ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)μg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

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