Periodontitis and vascular inflammatory biomarkers: an experimental in vivo study in rats

The objective of this preclinical in vivo study was to determine changes in vascular inflammatory biomarkers in systemic circulation after injection of lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) in rats. Experimental periodontitis was induced by injections of Pg-LPS. Gingival soft and hard tissues changes were analysed by means of magnetic resonance imaging and micro computed tomography. Serum levels of interleukin (IL)-6, IL-10, pentraxin (PTX) 3, and soluble fragment of tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were determined at baseline and 24 h, 7, 14, and 21 days after periodontal induction. Significant periodontal inflammation and alveolar bone loss were evident at the end of periodontal induction. Experimental periodontitis posed an acute systemic inflammatory response with increased serum levels of IL-6 and PTX3 at 24 h post-induction, followed by a significant overexpression of sTWEAK at 7 days. This inflammatory state was maintained until the end of the experiment (21 days). As expected, IL-10 serum levels were significantly lower during the follow-up compared to baseline concentrations. In the present animal model, experimental periodontitis is associated with increased systemic inflammation. Further studies are needed to confirm whether PTX3 and sTWEAK could be useful biomarkers to investigate potential mechanisms underlying the relationship between periodontitis and atherosclerotic vascular diseases

Genetic Analysis of Arrhythmogenic Diseases in the Era of NGS: The Complexity of Clinical Decision-Making in Brugada Syndrome

BACKGROUND: The use of next-generation sequencing enables a rapid analysis of many genes associated with sudden cardiac death in diseases like Brugada Syndrome. Genetic variation is identified and associated with 30-35% of cases of Brugada Syndrome, with nearly 20-25% attributable to variants in SCN5A, meaning many cases remain undiagnosed genetically. To evaluate the role of genetic variants in arrhythmogenic diseases and the utility of next-generation sequencing, we applied this technology to resequence 28 main genes associated with arrhythmogenic disorders. MATERIALS AND METHODS: A cohort of 45 clinically diagnosed Brugada Syndrome patients classified as SCN5A-negative was analyzed using next generation sequencing. Twenty-eight genes were resequenced: AKAP9, ANK2, CACNA1C, CACNB2, CASQ2, CAV3, DSC2, DSG2, DSP, GPD1L, HCN4, JUP, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNQ1, NOS1AP, PKP2, RYR2, SCN1B, SCN3B, SCN4B, SCN5A, SNTA1, and TMEM43. A total of 85 clinically evaluated relatives were also genetically analyzed to ascertain familial segregation. RESULTS AND DISCUSSION: Twenty-two patients carried 30 rare genetic variants in 12 genes, only 4 of which were previously associated with Brugada Syndrome. Neither insertion/deletion nor copy number variation were detected. We identified genetic variants in novel candidate genes potentially associated to Brugada Syndrome. These include: 4 genetic variations in AKAP9 including a de novo genetic variation in 3 positive cases; 5 genetic variations in ANK2 detected in 4 cases; variations in KCNJ2 together with CASQ2 in 1 case; genetic variations in RYR2, including a de novo genetic variation and desmosomal proteins encoding genes including DSG2, DSP and JUP, detected in 3 of the cases. Larger gene panels or whole exome sequencing should be considered to identify novel genes associated to Brugada Syndrome. However, application of approaches such as whole exome sequencing would difficult the interpretation for clinical purposes due to the large amount of data generated. The identification of these genetic variants opens new perspectives on the implications of genetic background in the arrhythmogenic substrate for research purposes. CONCLUSIONS: As a paradigm for other arrhythmogenic diseases and for unexplained sudden death, our data show that clinical genetic diagnosis is justified in a family perspective for confirmation of genetic causality. In the era of personalized medicine using high-throughput tools, clinical decision-making is increasingly complex

Tribological Behavior of Nanolubricants Based on Coated Magnetic Nanoparticles and Trimethylolpropane Trioleate Base Oil

The main task of this work is to study the tribological performance of nanolubricants formed by trimethylolpropane trioleate (TMPTO) base oil with magnetic nanoparticles coated with oleic acid: Fe3O4 of two sizes 6.3 nm and 10 nm, and Nd alloy compound of 19 nm. Coated nanoparticles (NPs) were synthesized via chemical co-precipitation or thermal decomposition by adsorption with oleic acid in the same step. Three nanodispersions of TMPTO of 0.015 wt% of each NP were prepared, which were stable for at least 11 months. Two different types of tribological tests were carried out: pure sliding conditions and rolling conditions (5% slide to roll ratio). With the aim of analyzing the wear by means of the wear scar diameter (WSD), the wear track depth and the volume of the wear track produced after the first type of the tribological tests, a 3D optical profiler was used. The best tribological performance was found for the Nd alloy compound nanodispersion, with reductions of 29% and 67% in friction and WSD, respectively, in comparison with TMPTO. On the other hand, rolling conditions tests were utilized to study friction and film thickness of nanolubricants, determining that Fe3O4 (6.3 nm) nanolubricant reduces friction in comparison to TMPTOThis research was supported by the Spanish Ministry of Economy and Competitiveness and the ERDF programme through the ENE2017-86425-C2-2-R project. Moreover, this work was funded by the Xunta de Galicia (ED431E 2018/08, GRC ED431C 2017/22 and GRC ED431C 2016/001). These three funders also financed the acquisition of the 3D Optical Profile Sensofar S Neox (UNST15-DE-3156)S

Cryptographic properties of Boolean functions defining elementary cellular automata

In this work, the algebraic properties of the local transition functions of elementary cellular automata (ECA) were analysed. Specifically, a classification of such cellular automata was done according to their algebraic degree, the balancedness, the resiliency, nonlinearity, the propagation criterion and the existence of non-zero linear structures. It is shown that there is not any ECA satisfying all properties at the same time

NGC 2419: a large and extreme second generation in a currently undisturbed cluster

We analyse complementary HST and SUBARU data for the globular cluster NGC 2419. We make a detailed analysis of the horizontal branch (HB), that appears composed by two main groups of stars: the luminous blue HB stars ---that extend by evolution into the RR Lyrae and red HB region--- and a fainter, extremely blue population. We examine the possible models for this latter group and conclude that a plausible explanation is that they correspond to a significant (~30 %) extreme second generation with a strong helium enhancement (Y~0.4). We also show that the color dispersion of the red giant branch is consistent with this hypothesis, while the main sequence data are compatible with it, although the large observational error blurs the possible underlying splitting. While it is common to find an even larger (50 -- 80) percentage of second generation in a globular cluster, the presence of a substantial and extreme fraction of these stars in NGC 2419 might be surprising, as the cluster is at present well inside the radius beyond which the galactic tidal field would be dominant. If a similar situation had been present in the first stages of the cluster life, the cluster would have retained its initial mass, and the percentage of second generation stars should have been quite small (up to ~10 %). Such a large fraction of extreme second generation stars implies that the system must have been initially much more massive and in different dynamical conditions than today. We discuss this issue in the light of existing models of the formation of multiple populations in globular clusters.Comment: 14 pages, 14 figures (5 in low resolution format), 3 tables, accepted for publication in MNRA

Sustained blood glutamate scavenging enhances protection in ischemic stroke

Stroke is a major cause of morbidity, mortality, and disability. During ischemic stroke, a marked and prolonged rise of glutamate concentration in the brain causes neuronal cell death. This study explores the protective effect of a bioconjugate form of glutamate oxaloacetate transaminase (hrGOT), which catalyzes the depletion of blood glutamate in the bloodstream for ~6 days following a single administration. When treated with this bioconjugate, a significant reduction of the infarct volume and a better retention of sensorimotor function was observed for ischemic rats compared to those treated with saline. Moreover, the equivalent dose of native hrGOT yielded similar results to the saline treated group for some tests. Targeting the bioconjugate to the blood-brain-barrier did not improve its performance. The data suggest that the bioconjugates draw glutamate out of the brain by displacing homeostasis between the different glutamate pools of the body

A detailed study of the main sequence of the Globular Cluster NGC 6397: can we derive constraints on the existence of multiple population?

If NGC 6397 contains a large fraction of "second generation" stars (>70% according to recent analysis), the helium abundance of its stars might also be affected, show some star-to-star variation, and be larger than the standard Big Bang abundance Y~0.24. Can we derive constraints on this issue from the analysis of the main sequence width and from its luminosity function? We build up new models for the turnoff masses and the main sequence down to the hydrogen burning minimum mass, adopting two versions of an updated equation of state (EOS) including the OPAL EOS. Models consider different initial helium and CNO abundances to cover the range of possible variations between the first and second generation stars. We compare the models with the observational main sequence. We also make simulations of the theoretical luminosity functions, for different choices of the mass function and of the mixture of first and second generation stars, and compare them with the observed luminosity function, by means of the Kolmogorov Smirnov --KS-- test. The study of the width of the main sequence at different interval of magnitude is consistent with the hypothesis that both generations are present in the cluster. If the CNO increase suggested by spectroscopic observation is taken into account the small helium spread of the main sequence in NGC 6397 implies a substantial helium uniformity (DY~0.02) between first and second generation stars. The possible spread in helium doubles if an even larger increase of CNO is considered. The luminosity function is in any case well consistent with the observed data.Comment: 13 pages, 13 figures, accepted for publication to A&

Calibrated stellar models for metal-poor population

We extend to lower metallicities recent evolutionary computations devoted to Magellanic Clouds stars, presenting and discussing new stellar models with Z=0.0002, 0.0004, 0.0006, 0.001 and suitable assumptions about the original He content. As in the previous paper, evolutionary results are compared with observational data to properly calibrate the assumptions about the efficiency of the surface convection. On this basis, we follow the evolution of stellar models in the mass range 0.6 to 11Mo from the Main Sequence (MS) to the C ignition or the onset of thermal pulses in the advanced Asymptotic Giant Branch (AGB) phase, presenting cluster isochrones covering the range of ages from 20 Myr to 20 Gyr. Selected predictions constraining the cluster ages are discussed, presenting a calibration of the difference in magnitude between the luminous MS termination and the He burning giants in terms of the cluster age. Both evolutionary tracks and isochrones are available at the URL http://astro.df.unipi.it/SAA/PEL/Z0.html. Data files are also available at the CDS.Comment: In publication on Astronomy and Astrophysic

Influence of Sex on Stroke Prognosis: A Demographic, Clinical, and Molecular Analysis

Identifying the complexities of the effect of sex on stroke risk, etiology, and lesion progression may lead to advances in the treatment and care of ischemic stroke (IS) and non-traumatic intracerebral hemorrhage patients (ICH). We studied the sex-related discrepancies on the clinical course of patients with IS and ICH, and we also evaluated possible molecular mechanisms involved. The study's main variable was the patient's functional outcome at 3-months. Logistic regression models were used in order to study the influence of sex on different inflammatory, endothelial and atrial dysfunction markers. We recruited 5,021 patients; 4,060 IS (54.8% male, 45.2% female) and 961 ICH (57.1% male, 42.9% female). Women were on average 5.7 years older than men (6.4 years in IS, 5.1 years in ICH), and more likely to have previous poor functional status, to suffer atrial fibrillation and to be on anticoagulants. IS patients showed sex-related differences at 3-months regarding poorer outcome (55.6% women, 43.6% men, p < 0.0001), but this relationship was not found in ICH (56.8% vs. 61.9%, p = 0.127). In IS, women had higher levels of NT-proBNP and 3-months worse outcome in both cardioembolic and non-cardioembolic stroke patients. Stroke patients showed sex-related differences in pre-hospital data, clinical variables and molecular markers, but only IS patients presented independent sex-related differences in 3-months poor outcome and mortality. There was a relationship between the molecular marker of atrial dysfunction NT-proBNP and worse functional outcome in women, resulting in a possible indicator of increased dysfunction

Regulatory T cells participate in the recovery of ischemic stroke patients

BACKGROUND: Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. METHODS: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale </=2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset. RESULTS: Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = - 0.414) and 72 h (r = - 0.418) and infarct volume. CONCLUSIONS: These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke