Cyclooxygenase Inhibition Safety and Efficacy in Inflammation-Based Psychiatric Disorders

According to the World Health Organization, the major psychiatric and neurodevelopmental disorders include major depression, bipolar disorder, schizophrenia, and autism spectrum disorder. The potential role of inflammation in the onset and progression of these disorders is increasingly being studied. The use of non-steroidal anti-inflammatory drugs (NSAIDs), well-known cyclooxygenase (COX) inhibitors, combined with first-choice specific drugs have been long investigated. The adjunctive administration of COX inhibitors to classic clinical treatments seems to improve the prognosis of people who suffer from psychiatric disorders. In this review, a broad overview of the use of COX inhibitors in the treatment of inflammation-based psychiatric disorders is provided. For this purpose, a critical analysis of the use of COX inhibitors in the last ten years of clinical trials of the major psychiatric disorders was carried out

K Index in cerebrospinal fluid: a valid tool in multiple sclerosis diagnosis

Detection of oligoclonal IgG bands in cerebrospinal fluid by isoelectrocfocusing and immunodetection is the current gold standard to detect an inflammatory process in the central nervous system. It has been proposed that the presence of free light chains (FLCs) in CSF was associated with recent demyelination activity in MS and might be used as a prognosis marker. Our study’s objective is assessing the diagnostic accuracy of a new highly sensitive latex-enhanced nephelometric assay for k free light chain (kFLC) determination in CSF/serum as an alternative to traditional tests and its clinical application. Methods. kFLCs were measured in CSF/serum pairs from 80 patients by the use of a new highly sensitive latex-enhanced nephelometric automated immunoassay for detection of immunoglobulin FLC. The eighty patients were split into three groups according to the neurological diagnosis. In this study we confirm even more the use of the k Index as a diagnostic aid in multiple sclerosis. Results. kFLC Index seems to be more accurate parameter respect the determination of oligoclonal immunoglobulin bands (OCBs). We recalculate the K Index sensitivity and specificity respect the precedent published result. Two patients previously diagnosed with leukoencephalopathy have gone to group 3 as confirmed the diagnosis of MS. Conclusions. These new data reinforce even more the use of the k Index to diagnose MS in comparison to classical methods and to the reference method, the OCBs

The Link Among Neurological Diseases: Extracellular Vesicles as a Possible Brain Injury Footprint

Extracellular vesicles (EVs), referred as membranous vesicles released into body fluids from all cell types, represent a novel model to explain some aspects of the inter-cellular cross talk. It has been demonstrated that the EVs modify the phenotype of target cells, acting through a large spectrum of mechanisms. In the central nervous system, the EVs are responsible of the wide range of physiological processes required for normal brain function and neuronal support, such as immune signaling, cellular proliferation, differentiation, and senescence. Growing evidences link the EV functions to the pathogenic machinery of the neurological diseases, contributing to the disease progression and spreading. Extracellular vesicles are involved in the brain injury by multimodal ways; they propagate inflammation across the blood brain barrier (BBB), mediate neuroprotection and modulate regenerative processes. For these reasons, extracellular vesicles represent a promising biomarker in neurological disorders as well as an interesting starting point for the development of novel therapeutic strategies. Herein, we review the role of the EVs in the pathogenesis of neurological disease, discussing their potential clinical applications

Improving cuff-less continuous blood pressure estimation with linear regression analysis

In this work, the authors investigate the cuff-less estimation of continuous BP through pulse transit time (PTT) and heart rate (HR) using regression techniques, which is intended as a first step towards continuous BP estimation with a low error, according to AAMI guidelines. Hypertension (the 'silent killer') is one of the main risk factors for cardiovascular diseases (CVDs), which are the main cause of death worldwide. Its continuous monitoring can offer a valid tool for patient care, as blood pressure (BP) is a significant indicator of health and, using it together with other parameters, such as heart and breath rates, could strongly improve prevention of CVDs. The novelties introduced in this work are represented by the implementation of pre-processing and by the innovative method for features research and features processing to continuously monitor blood pressure in a non-invasive way. Currently, invasive methods are the only reliable methods for continuous monitoring, while non-invasive techniques measure the values every few minutes. The proposed approach can be considered the first step for the integration of these types of algorithms on wearable devices, in particular on those developed for the SINTEC project

Differential ttbar cross-section measurements using boosted top quarks in the all-hadronic final state with 139 fb-1 of ATLAS data

Measurements of single-, double-, and triple-differential cross-sections are presented for boosted top-quark pair-production in 13 TeV proton–proton collisions recorded by the ATLAS detector at the LHC. The top quarks are observed through their hadronic decay and reconstructed as large-radius jets with the leading jet having transverse momentum (pT) greater than 500 GeV. The observed data are unfolded to remove detector effects. The particle-level cross-section, multiplied by the t¯t ! WWb¯b branching fraction and measured in a fiducial phase space defined by requiring the leading and second-leading jets to have pT > 500 GeV and pT > 350 GeV, respectively, is 331 ± 3(stat.) ± 39(syst.) fb. This is approximately 20% lower than the prediction of 398+48−49 fb by Powheg+Pythia 8 with next-to-leading-order (NLO) accuracy but consistent within the theoretical uncertainties. Results are also presented at the parton level, where the effects of top-quark decay, parton showering, and hadronization are removed such that they can be compared with fixed-order next-to-next-to-leading-order (NNLO) calculations. The partonlevel cross-section, measured in a fiducial phase space similar to that at particle level, is 1.94 ± 0.02(stat.) ± 0.25(syst.) pb. This agrees with the NNLO prediction of 1.96+0.02−0.17 pb. Reasonable agreement with the differential cross-sections is found for most NLO models, while the NNLO calculations are generally in better agreement with the data. The differential cross-sections are interpreted using a Standard Model effective field-theory formalism and limits are set on Wilson coefficients of several four-fermion operators

Measurement of the polarisation of single top quarks and antiquarks produced in the t-channel at sqrt(s) = 13 TeV and bounds on the tWb dipole operator from the ATLAS experiment

A simultaneous measurement of the three components of the top-quark and top-antiquark polarisation vectors in t-channel single-top-quark production is presented. This analysis is based on data from proton-proton collisions at a centre-of-mass energy of 13 TeV corresponding to an integrated luminosity of 139 fb(-1), collected with the ATLAS detector at the LHC. Selected events contain exactly one isolated electron or muon, large missing transverse momentum and exactly two jets, one being b-tagged. Stringent selection requirements are applied to discriminate t-channel single-top-quark events from the background contributions. The top-quark and top-antiquark polarisation vectors are measured from the distributions of the direction cosines of the charged-lepton momentum in the top-quark rest frame. The three components of the polarisation vector for the selected top-quark event sample are P-x' = 0.01 +/- 0.18, P-y' = -0.029 +/- 0.027, P-z' = 0.91 +/- 0.10 and for the top-antiquark event sample they are P-x' = -0.02 +/- 0.20, P-y' = -0.007 +/- 0.051, P-z' = -0.79 +/- 0.16. Normalised differential cross-sections corrected to a fiducial region at the stable-particle level are presented as a function of the charged-lepton angles for top-quark and top-antiquark events inclusively and separately. These measurements are in agreement with Standard Model predictions. The angular differential cross-sections are used to derive bounds on the complex Wilson coefficient of the dimension-six O-tW operator in the framework of an effective field theory. The obtained bounds are C-tW is an element of[-0.9, 1.4] and C-itW is an element of [-0.8, 0.2], both at 95% confidence level

TLR3 expression induces apoptosis in human non‐small‐cell lung cancer

The prognostic value of Toll\u2010like receptor 3 (TLR3) is debated in cancer, differing between tumor types, methods, and cell types. We recently showed for the first time that TLR3 expression on early stage non\u2010small\u2010cell lung cancer (NSCLC) results associated with a good prognosis. Here, we provide experimental evidences explaining the molecular reason behind TLR3\u2019s favorable prognostic role. We demonstrated that TLR3 activation in vitro induces apoptosis in lung cancer cell lines and, accordingly, that TLR3 expression is associated with caspase\u20103 activation in adenocarcinoma NSCLC specimens, both evaluated by immunohistochemistry. Moreover, we showed that TLR3 expression on cancer cells contributes to activate the CD103+ lung dendritic cell subset, that is specifically associated with processing of antigens derived from apoptotic cells and their presentation to CD8+ T lymphocytes. These findings point to the relevant role of TLR3 expression on lung cancer cells and support the use of TLR3 agonists in NSCLC patients to re\u2010activate local innate immune response

Measurement of substructure-dependent jet suppression in Pb+Pb collisions at 5.02 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider has been used to measure jet substructure modification and suppression in Pb+Pb collisions at a nucleon–nucleon center-of-mass energy sqrt(sNN) = 5.02 TeV in comparison with proton–proton (pp) collisions at sqrt(s) = 5.02 TeV. The Pb+Pb data, collected in 2018, have an integrated luminosity of 1.72 nb−1, while the pp data, collected in 2017, have an integrated luminosity of 260 pb−1. Jets used in this analysis are clustered using the anti-kt algorithm with a radius parameter R = 0.4. The jet constituents, defined by both tracking and calorimeter information, are used to determine the angular scale rg of the first hard splitting inside the jet by reclustering them using the Cambridge–Aachen algorithm and employing the softdrop grooming technique. The nuclear modification factor, RAA, used to characterize jet suppression in Pb+Pb collisions, is presented differentially in rg, jet transverse momentum, and in intervals of collision centrality. The RAA value is observed to depend significantly on jet rg. Jets produced with the largest measured rg are found to be twice as suppressed as those with the smallest rg in central Pb+Pb collisions. The RAA values do not exhibit a strong variation with jet pT in any of the rg intervals. The rg and pT dependence of jet RAA is qualitatively consistent with a picture of jet quenching arising from coherence and provides the most direct evidence in support of this approach

Measurement of the nuclear modification factor of b-jets in 5.02 TeV Pb+Pb collisions with the ATLAS detector

This paper presents a measurement of b-jet production in Pb+Pb and pp collisions at sqrt(sNN) = 5.02 TeV with the ATLAS detector at the LHC. The measurement uses 260 pb−1 of pp collisions collected in 2017 and 1.4 nb−1 of Pb+Pb collisions collected in 2018. In both collision systems, jets are reconstructed via the anti-kt algorithm. The b-jets are identified from a sample of jets containing muons from the semileptonic decay of b-quarks using template fits of the muon momentum relative to the jet axis. In pp collisions, b-jets are reconstructed for radius parameters R=0.2 and R=0.4, and only R=0.2 jets are used in Pb+Pb collisions. For comparison, inclusive R=0.2 jets are also measured using 1.7 nb−1 of Pb+Pb collisions collected in 2018 and the same pp collision data as the b-jet measurement. The nuclear modification factor, RAA, is calculated for both b-jets and inclusive jets with R=0.2 over the transverse momentum range of 80–290 GeV. The nuclear modification factor for b-jets decreases from peripheral to central collisions. The ratio of the b-jet RAA to inclusive jet RA is also presented and suggests that the RAA for b-jets is larger than that for inclusive jets in central Pb+Pb collisions. The measurements are compared with theoretical calculations and suggest a role for mass and colour-charge effects in partonic energy loss in heavy-ion collisions

Correlations between flow and transverse momentum in Xe+Xe and Pb+Pb collisions at the LHC with the ATLAS detector: A probe of the heavy-ion initial state and nuclear deformation

The correlations between flow harmonics vn for n = 2, 3, and 4 and mean transverse momentum [pT] in 129Xe+129Xe and 208Pb+208Pb collisions at sqrt(s) = 5.44 and 5.02 TeV, respectively, are measured using charged particles with the ATLAS detector. The correlations are potentially sensitive to the shape and size of the initial geometry, nuclear deformation, and initial momentum anisotropy. The effects from nonflow and centrality fluctuations are minimized, respectively, via a subevent cumulant method and an event-activity selection based on particle production at very forward rapidity. The vn-[pT] correlations show strong dependencies on centrality, harmonic number n, pT, and pseudorapidity range. Current models qualitatively describe the overall centrality and system-dependent trends but fail to quantitatively reproduce all features of the data. In central collisions, where models generally show good agreement, the v2-[pT] correlations are sensitive to the triaxiality of the quadruple deformation. Comparison of the model with the Pb + Pb and Xe + Xe data confirms that the 129Xe nucleus is a highly deformed triaxial ellipsoid that has neither a prolate nor oblate shape. This provides strong evidence for a triaxial deformation of the 129Xe nucleus from high-energy heavy-ion collisions