Polymorphonuclear cells and reactive oxygen species in contagious bovine pleuropneumonia: New insight from in vitro investigations

Abstract Reactive oxygen species (ROS) are suggested to play a role in the pathogenesis of contagious bovine pleuropneumonia, a severe respiratory disorder caused by Mycoplasma mycoides subsp. mycoides ( Mmm ). The present study investigated the generation of ROS by different strains of Mmm , as well as their effect on the oxidative response of bovine neutrophils. The production of ROS was indirectly measured using a luminol-based chemiluminescence assay. Our results confirm that Mmm can produce ROS via the metabolism of glycerol, significant differences existing between African and European strains. Mmm was capable of adhering to the external surface of neutrophils. Interestingly, Mmm enhanced the respiratory burst of bovine neutrophils. This activity was particularly pronounced with the African field strain and in presence of glycerol. Taken together, our data argue in favour of a major role for neutrophils as the main source of ROS in contagious bovine pleuropneumonia

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a transversal challenge. The INVIDIa study

Aim: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. Methods: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017. Results: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001. Conclusion: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

Gaia Early Data Release 3: Structure and properties of the Magellanic Clouds

We compare the Gaia DR2 and Gaia EDR3 performances in the study of the Magellanic Clouds and show the clear improvements in precision and accuracy in the new release. We also show that the systematics still present in the data make the determination of the 3D geometry of the LMC a difficult endeavour; this is at the very limit of the usefulness of the Gaia EDR3 astrometry, but it may become feasible with the use of additional external data. We derive radial and tangential velocity maps and global profiles for the LMC for the several subsamples we defined. To our knowledge, this is the first time that the two planar components of the ordered and random motions are derived for multiple stellar evolutionary phases in a galactic disc outside the Milky Way, showing the differences between younger and older phases. We also analyse the spatial structure and motions in the central region, the bar, and the disc, providing new insights into features and kinematics. Finally, we show that the Gaia EDR3 data allows clearly resolving the Magellanic Bridge, and we trace the density and velocity flow of the stars from the SMC towards the LMC not only globally, but also separately for young and evolved populations. This allows us to confirm an evolved population in the Bridge that is slightly shift from the younger population. Additionally, we were able to study the outskirts of both Magellanic Clouds, in which we detected some well-known features and indications of new ones

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Lung lesion score system in cattle: proposal for contagious bovine pleuropneumonia

Contagious bovine pleuropneumonia (CBPP) is a severe infectious disease caused by Mycoplasma mycoides subsp. mycoides. The peculiar pathological features of CBPP make desirable the assessment of ad hoc score methods to grade the disease in the affected animals. Thus, the present work aims to assess a new lung score system for CBPP. Our results indicate that the present score system strongly correlates with that previously published by Turner and could be effectively used in CBPP-affected animals

Microstructure and Wear Behavior of Plasma-Sprayed Nanostructured WC-Co Coatings

Atmospheric plasma spraying of WCCo particles with standard gas mixtures (ArH2) typically results in largely decarburized coatings with relatively low wear resistance. To fabricate cermet coatings with enhanced tribological properties, nanostructured WCCo coatings were plasma sprayed using two different process gas mixtures. Phase composition and microstructure were investigated by X-ray diffraction and scanning electron microscopy, respectively. Microhardness increased by increasing the amount of retained WC grains in coating microstructure. Friction and wear properties, measured under dry sliding conditions, strongly depended on the degree of decarburization. They were comparable to those of conventional coatings produced using identical conditions

Modellizzazione DIB-FEA del comportamento meccanico di ceramici cellulari

Nel presente lavoro si suggerisce l’impiego di un’analisi agli elementi finiti assistita da tecniche di analisi di immagine digitale per la modellizzazione del comportamento meccanico di solidi ceramici cellulari. Sulla base dei dati relativi alle proprietà meccaniche del materiale denso ottenuti da prove di compressione, si è simulato, a partire da immagini rappresentative di varie microstrutture, il comportamento meccanico di campioni di materiale ceramico cellulare (idrossiapatite gel-casting). I risultati preliminari mostrano un buon accordo coi dati sperimentali di riscontro e confermano l’interesse verso i metodi DIB-FEA.In this paper we suggest the use of a finite element analysis assisted by digital image analysis techniques for the modeling of the mechanical behavior of solid ceramic phones. On the basis of data on the mechanical properties of the dense material obtained from compression tests, was simulated, starting with representative images of various microstructures, the mechanical behavior of samples of cellular ceramic material (hydroxyapatite gel-casting). Preliminary results show a good agreement with the experimental data matching and confirm the interest in the DIB-FEA methods

Evolution of microstructural and mechanical properties of lanthanum zirconate thermal barrier coatings at high temperature

Ceramic thermal barrier coatings (TBCs) are advanced systems for more efficient turbine engines. In this work, thick lanthanum zirconate TBCs were fabricated by Air Plasma Spraying (APS). The coatings showed a lamellar microstructure containing splat boundaries, pores and microcracks. After thermal exposure at 1200 and 1350 degrees C the partial sintering of the porous microstructure occurred. High-temperature evolution of the mechanical properties was investigated by arranging specific bending tests up to 1500 degrees C using SiC testing assembly which allowed to calculate the strain by means of curvature measurement. The mechanical properties improved with increasing the testing temperature, due to the inelastic deformation and stress relaxation which counteracted the sintering effects. The elastic modulus increased after thermal aging, but decreased for the aged coatings tested at higher temperature. The thermal expansion coefficient of as-sprayed coatings slightly increased after thermal aging, while a reduction of specific heat capacity was noticed. (C) 2014 Elsevier B.V. All rights reserved