Glycan affinity magnetic nanoplatforms for urinary glycobiomarkers discovery in bladder cancer

Bladder Cancer (BC) presents one of the highest recurrence rates amongst solid tumours and constitutes the second deadliest disease of the genitourinary track. Non-invasive identification of patients facing disease recurrence and/or progression remains one of the most critical and challenging aspects in disease management. To contribute to this goal, we demonstrate the potential of glycan-affinity glycoproteomics nanoplatforms for urinary biomarkers discovery in bladder cancer. Briefly, magnetic nanoprobes (MNP) coated with three broad-spectrum lectins, namely Concanavalin A (ConA; MNP@ConA), Wheat Germ Agglutinin (WGA; MNP@WGA), and Sambucus nigra (SNA; MNP@SNA), were used to selectively capture glycoproteins from the urine of low-grade and high-grade non-muscle invasive as well as muscle-invasive BC patients. Proteins were identified by nano-LC MALDI-TOF/TOF and data was curated using bioinformatics tools (UniProt, NetOGlyc, NetNGlyc, ClueGO app for Cytoscape and Oncomine) to highlight clinically relevant species. Accordingly, 63 glycoproteins were exclusively identified in cancer samples compared with healthy controls matching in age and gender. Specific glycoprotein sets exclusively found in low-grade non-muscle invasive bladder tumours may aid early diagnosis, while those only found in high-grade non-invasive and muscle-invasive tumours hold potential for accessing progression. Amongst these proteins is bladder cancer stem-cell marker CD44, which has been associated with poor prognosis. Orthogonal validation studies by slot-blotting demonstrated an elevation in urine CD44 levels of high-grade patients, which became more pronounced upon muscle-invasion, in mimicry of the primary tumour. These observations demonstrate the potential of MNP@lectins for identification of clinically relevant glycoproteomics signatures in bladder cancer. Future clinical validation in a larger and well characterized patient subset is required envisaging clinical translation of the results.publishe

DELETERIOUS EFFECT OF HIGH CARNOSINE CONCENTRATIONS IN EXTENDERS DURING SPERM CRYOPRESERVATION IN DOGS / EFECTO DELETÉREO DE ALTAS CONCENTRACIONES DE CARNOSINA EN DILUYENTES DURANTE LA CRIOPRESERVACIÓN ESPERMÁTICA EN PERROS

Cryopreservation is a key process among the canine reproductive biotechnologies. However, during sperm cryopreservation an excessive reactive oxygen species (ROS) generation occurs, leading to decrease in sperm quality. Therefore, several antioxidants were tested during sperm cryopreservation to prevent such effects, however the carnosine it has not used. Carnosine is a protein present in the seminal plasma, and unlike other antioxidants has the ability to remove products of lipid peroxidation (malondialdehyde), which are as harmful as ROS. Thus, the aim of this study was to evaluate the effects of different carnosine concentrations, during sperm cryopreservation in dogs. For this purpose, six dogs in reproductive age were used, and after sperm collection the samples were cryopreserved in Control (tris-citrate egg yolk extender), Carnosine 1mM, 50mM and 100mM groups. After thawing samples were analyzed by computer-assisted analysis of sperm motility, plasma membrane (eosin/nigrosin), acrosome integrity (fast green/rose Bengal), mitochondrial activity, DNA integrity and sperm resistance to oxidative stress (by TBARS). Decrease was observed in motility sperm kinetics (total and progressive motility) and reduced lipid peroxidation products in the group treated with 50mM and 100mM. On the other hand, 1mM was similar to control group. In conclusion, higher carnosine concentration (50 and 100mM) apparently promoted impairment in energy production and consequently was harmful to sperm kinetics. Thus, future studies must be performed using different carnosine concentrations and in association with substrates for glycolysis and oxidative phosphorylation.RESUMENLa criopreservación es un proceso clave entre las biotecnologías reproductivas en caninos. Sin embargo, durante la criopreservación espermática se da una generación excesiva de especies reactivas de oxígeno (ROS), lo que lleva a una disminución en la calidad espermática. Por lo tanto, varios medios de congelación utilizando antioxidantes para evitar tales efectos han sido evaluados, aunque la carnosina todavía no se ha utilizada. La carnosina es una proteína presente en el plasma seminal que a diferencia de otros antioxidantes tiene la habilidad de remover productos de la peroxidación lipídica (malondialdehído), que son tan dañinos como los ROS. Por lo tanto, el objetivo de este estudio fue evaluar los efectos de diferentes concentraciones de carnosina durante la congelación espermática en perros. Para este propósito se utilizaron seis perros en edad reproductiva y después de la colectar los eyaculados, las muestras fueron criopreservadas en un diluyente Control (tris, citrato, yema de huevo), Carnosina 1mM, 50mM y 100 mM. Después del descongelado, las muestras fueron evaluadas mediante el análisis computerizado de la motilidad, integridad de membrana plasmática (eosina / nigrosina), integridad del acrosoma (Fast - green / rosa de Bengala), la actividad mitocondrial (3’3 Diaminobenzidina), la integridad del ADN (SCSA) y la evaluación de la resistencia al estrés oxidativo (TBARS). Se observó una disminución en la cinética de los espermatozoides (motilidad total y progresiva) y una reducción de los productos de la peroxidación lipídica en los grupos tratados con 50 mM y 100mM de carnosina. Por otro lado, el grupo con 1 mM de carnosina fue similar al control. En conclusión, una alta concentración de carnosina (50 y 100mM) parece afectar la producción de energía del espermatozoide y por lo tanto es perjudicial para la cinética del espermatozoide. Por lo tanto, futuros estudios deben realizarse utilizando diferentes concentraciones de carnosina y en asociación con sustratos para la glucólisis y la fosforilación oxidativa

Thrombus aspiration in patients with ST-elevation myocardial infarction: results of a national registry of interventional cardiology

BACKGROUND: We aimed to evaluate the impact of thrombus aspiration (TA) during primary percutaneous coronary intervention (P-PCI) in 'real-world' settings. METHODS: We performed a retrospective study, using data from the National Registry of Interventional Cardiology (RNCI 2006-2012, Portugal) with ST-elevation myocardial infarction (STEMI) patients treated with P-PCI. The primary outcome, in-hospital mortality, was analysed through adjusted odds ratio (aOR) and 95% confidence intervals (95%CI). RESULTS: We assessed data for 9458 STEMI patients that undergone P-PCI (35% treated with TA). The risk of in-hospital mortality with TA (aOR 0.93, 95%CI:0.54-1.60) was not significantly decreased. After matching patients through the propensity score, TA reduced significantly the risk of in-hospital mortality (OR 0.58, 95%CI:0.35-0.98; 3500 patients). CONCLUSIONS: The whole cohort data does not support the routine use of TA in P-PCI, but the results of the propensity-score matched cohort suggests that the use of selective TA may improve the short-term risks of STEMI..info:eu-repo/semantics/publishedVersio

Determinants of HIV late presentation among men who have sex with men in Portugal (2014–2019): who’s being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.info:eu-repo/semantics/publishedVersio

Updated cardiovascular prevention guideline of the Brazilian Society of Cardiology: 2019

Sem informação113478788

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe