Effects of sodium benzoate on the innate immune response to gram-negative bacteria and Toll-like receptor stimulation

Sodium benzoate (NaB) is a sodium salt that is widely used in the pharmaceutical, cosmetic and food industries. This widespread use results in almost everybody in the world being exposed daily to this compound. Currently very little is known about the effects of NaB can have on the immune response, even though it has been associated with the clinical course of chronic inflammatory diseases, such as orofacial granulomatosis and neurodegenerative disorders. Here, I show that THP-1 cells, a monocytic human cell line presents an altered immune response when exposed to NaB. Immunologically stimulated THP-1 cells in the presence of NaB secreted reduced levels of IL6 and IL1β and higher levels of TNF, while other cytokines such as IP10 and IL8 were unaffected. The inhibitory effect in IL6 and IL1β secretion was a consequence of a free radical scavenging characteristic of NaB, which neutralizes the reactive oxygen species (ROS) generated downstream of TLR activation. This resulted in the impairment of a secondary signalling event, which is required to fully activate the cells immune response. The use of microarray analysis in combination with q quantitative proteomic analysis revealed that NaB has a significant effect on the THP-1 cells beyond the alteration in cytokine secretion. NaB also interferes with cellular amino acid metabolism and has a major attenuating effect on the immune response. Taken together, these results suggest that NaB is not inert and has a major effect on a cells ability to mount an immune response. These findings could have major implications in how NaB is used in the future and in particular if it can be beneficial as a treatment for chronic inflammatory diseases, such as diabetes, atherosclerosis, rheumatoid arthritis, neurodegenerative disorders, and so on. On the other hand, by disturbing the inflammatory response, NaB could have a negative impact on other conditions such as orofacial granulomatosis. Further work will be needed to determine the role NaB plays in human inflammatory diseases

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.This work was primarily supported by grant OPP1132415 from the Bill & Melinda Gates Foundatio

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

Chikungunya virus and its envelope protein E2 induce hyperalgesia in mice: Inhibition by anti-E2 monoclonal antibodies and by targeting TRPV1

Chikungunya virus is an arthropod-borne infectious agent that causes Chikungunya fever disease. About 90% of the infected patients experience intense polyarthralgia, affecting mainly the extremities but also the large joints such as the knees. Chronic disease symptoms persist for months, even after clearance of the virus from the blood. Envelope proteins stimulate the immune response against the Chikungunya virus, becoming an important therapeutic target. We inactivated the Chikungunya virus (iCHIKV) and produced recombinant E2 (rE2) protein and three different types of anti-rE2 monoclonal antibodies. Using these tools, we observed that iCHIKV and rE2 protein induced mechanical hyperalgesia (electronic aesthesiometer test) and thermal hyperalgesia (Hargreaves test) in mice. These behavioral results were accompanied by the activation of dorsal root ganglia (DRG) neurons in mice, as observed by calcium influx. Treatment with three different types of anti-rE2 monoclonal antibodies and absence or blockade (AMG-9810 treatment) of transient receptor potential vanilloid 1 (TRPV1) channel diminished mechanical and thermal hyperalgesia in mice. iCHIKV and rE2 activated TRPV1+ mouse DRG neurons in vitro, demonstrating their ability to activate nociceptor sensory neurons directly. Therefore, our mouse data demonstrate that targeting E2 CHIKV protein with monoclonal antibodies and inhibiting TRPV1 channels are reasonable strategies to control CHIKV pain

Study of the electron trigger efficiency of the CMS Experiment using test beam data

A study of the electron identification and selection efficiency of the L1 Trigger algorithm has been performed using the combined ECAL/HCAL test beam data. A detailed discussion of the electron isolation and its impact on the selection efficiency is presented. The L1 electron algorithm is studied for different beam energies and the results indicate that efficiencies of 98% or more can be achieved for electrons with energies between 15 and 100 GeV. The fraction of charged hadrons with energies from 3 up to 100 GeV rejected by the L1 electron trigger algorithm is estimated to be larger than 93%.Comment: 22 pages, 14 figure

Paradoxical Pulmonary Event Under Tocilizumab Treatment for Systemic Sclerosis-Associated Usual Interstitial Pneumonia

info:eu-repo/semantics/publishedVersio

Association Between Glycated Albumin, Fructosamine, and HbA1c with Neonatal Outcomes in a Prospective Cohort of Women with Gestational Diabetes Mellitus

Objective: To investigate whether glycated albumin, fructosamine, and hemoglobin A1c (HbA1c) are associated with neonatal complications in newborns of pregnant women with gestational diabetes mellitus (GDM). Methods: Between November 2016 and September 2017, women with a singleton pregnancy and GDM were enrolled in a prospective study in an obstetric Portuguese referral center. Glycemic markers were compared between mothers of newborns with and without complications. Multivariable logistic regression models and corresponding areas under the receiver operating characteristic curve (AUC) were used. Results: A total of 85 women participated in the study. Raised levels of glycated albumin and fructosamine were associated with at least one neonatal complication (OR- [odds ratio] estimate: 1.33, P=0.015; OR: 1.24, P=0.027, respectively) and with respiratory disorders at birth (OR 1.41, P=0.004; OR 1.26, P=0.014, respectively). HbA1c was not associated with these outcomes. All biomarkers were associated with large-for-gestational age (LGA) status (OR 1.61, P<0.001; OR 1.45, P<0.001; OR 3.62, P=0.032 for glycated albumin, fructosamine, and HbA1c, respectively). All had similar AUC for at least one neonatal complication (0.82; 0.81; 0.79, respectively). For newborn respiratory disorders, AUCs were 0.83, 0.81, and 0.76, respectively, and for LGA status were 0.81, 0.79, and 0.71, respectively. Conclusion: Raised values of glycated albumin and fructosamine were associated with particular perinatal complications in newborns of mothers with GDM, better discriminating mothers of newborns with and without complications than HbA1c.info:eu-repo/semantics/publishedVersio

Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms

BACKGROUND: Lipoxin A4 (LXA METHODS: Mice were stimulated with TiO RESULTS: LXA CONCLUSION: LX