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Magnetic resonance (MR) with sodium (23Na) is a noninvasive tool providing quantitative biochemical information regarding physiology, cellular metabolism, and viability, with the potential to extend MR beyond anatomical proton imaging. However, when using clinical scanners, the low detectable 23Na signal and the low 23Na gyromagnetic ratio require the design of dedicated radiofrequency (RF) coils tuned to the 23Na Larmor frequency and sequences, as well as the development of dedicated phantoms for testing the image quality, and an MR scanner with multinuclear spectroscopy (MNS) capabilities. In this work, we propose a hardware and software setup for evaluating the potential of 23Na magnetic resonance imaging (MRI) with a clinical scanner. In particular, the reliability of the proposed setup and the reproducibility of the measurements were verified by multiple acquisitions from a 3T MR scanner using a homebuilt RF volume coil and a dedicated sequence for the imaging of a phantom specifically designed for evaluating the accuracy of the technique. The final goal of this study is to propose a setup for standardizing clinical and research 23Na MRI protocols.

Background and aims: Genetic testing is still rarely used for the diagnosis of dyslipidemia, even though gene variants determining plasma lipids levels are not uncommon. Methods: Starting from a a pilot-analysis of targeted Next Generation Sequencing (NGS) of 5 genes related to familial hypercholesterolemia (LDLR, APOB, PCSK9, HMGCR, APOE) within a cardiovascular cohort in subjects with extreme plasma concentrations of low-density lipoprotein (LDL) cholesterol, we discovered and characterized a novel point mutation in the APOB gene, which was associated with very low levels of apolipoprotein B (ApoB) and LDL cholesterol. Results: APOB c.6943 G > T induces a premature stop codon at the level of exon 26 in the APOB gene and generates a protein which has the 51% of the mass of the wild type ApoB-100 (ApoB-51), with a truncation at the level of residue 2315. The premature stop codon occurs after the one needed for the synthesis of ApoB-48, allowing chylomicron production at intestinal level and thus avoiding potential nutritional impairments. The heterozygous carrier of APOB c.6943G > T, despite a very high-risk profile encompassing all the traditional risk factors except for dyslipidemia, had normal coronary arteries by angiography and did not report any major adverse cardiovascular event during a 20-years follow-up, thereby obtaining advantage from the gene variant as regards protection against atherosclerosis, apparently without any metabolic retaliation. Conclusions: Our data support the use of targeted NGS in well-characterized clinical settings, as well as they indicate that.a partial block of ApoB production may be well tolerated and improve cardiovascular outcomes.

Abstract Quantitative susceptibility mapping (QSM) is a powerful, non-invasive, magnetic resonance imaging (MRI) technique that relies on measurement of magnetic susceptibility. So far, QSM has been employed mostly to study neurological disorders characterized by iron accumulation, such as Parkinson’s and Alzheimer’s diseases. Nonetheless, QSM allows mapping key indicators of cardiac disease such as blood oxygenation and myocardial iron content. For this reason, the application of QSM offers an unprecedented opportunity to gain a better understanding of the pathophysiological changes associated with cardiovascular disease and to monitor their evolution and response to treatment. Recent studies on cardiovascular QSM have shown the feasibility of a non-invasive assessment of blood oxygenation, myocardial iron content and myocardial fibre orientation, as well as carotid plaque composition. Significant technical challenges remain, the most evident of which are related to cardiac and respiratory motion, blood flow, chemical shift effects and susceptibility artefacts. Significant work is ongoing to overcome these challenges and integrate the QSM technique into clinical practice in the cardiovascular field.

BackgroundUrinary extracellular vesicles (uEVs) can be released by different cell types facing the urogenital tract and are involved in cellular trafficking, differentiation and survival. UEVs can be easily detected in urine and provide pathophysiological information “in vivo” without the need of a biopsy. Based on these premises, we hypothesized that uEVs proteomic profile may serve as a valuable tool in the differential characterization between Essential Hypertension (EH) and primary aldosteronism (PA).MethodsPatients with essential hypertension (EH) and PA were enrolled in the study (EH= 12, PA=24: 11 Bilateral Primary Aldosteronism subtype (BPA) and 13 Aldosterone Producing Adenoma (APA)). Clinical and biochemical parameters were available for all the subjects. UEVs were isolated from urine by ultracentrifugation and analysed by Transmission Electron Microscopy (TEM) and nanotrack particle analysis (NTA). UEVs protein content was investigated through an untargeted MS-based approach. Statistical and network analysis was performed to identify potential candidates for the identification and classification of PA.ResultsMS analysis provided more than 300 protein identifications. Exosomal markers CD9 and CD63 were detected in all samples. Several molecules characterizing EH vs PA patients as well as BPA and APA subtypes were identified after statistical elaboration and filtering of the results. In particular, some key proteins involved in water reabsorption mechanisms, such as AQP1 and AQP2, were among the best candidates for discriminating EH vs PA, as well as A1AG1 (AGP1).ConclusionThrough this proteomic approach, we identified uEVs molecular indicators that can improve PA characterization and help in the gain of insights of the pathophysiological features of this disease. In particular, PA was characterized by a reduction of AQP1 and AQP2 expression as compared with EH.

Abstract Left ventricular (LV) remodeling after myocardial infarction (MI) is promoted by an intense fibrotic response, which could be targeted by the anti-fibrotic drug pirfenidone. We explored the relationship between protein modulation by pirfenidone and post-MI remodeling, based on molecular information and transcriptomic data from a swine model of MI. We identified 6 causative motives of post-MI remodeling (cardiomyocyte cell death, impaired myocyte contractility, extracellular matrix remodeling and fibrosis, hypertrophy, renin–angiotensin–aldosterone system activation, and inflammation), 4 pirfenidone targets and 21 bioflags (indirect effectors). Pirfenidone had a more widespread action than gold-standard drugs, encompassing all 6 motives, with prominent effects on p38γ-MAPK12, the TGFβ1-SMAD2/3 pathway and other effector proteins such as matrix metalloproteases 2 and 14, PDGFA/B, and IGF1. A bioinformatic approach allowed to identify several possible mechanisms of action of pirfenidone with beneficial effects in the post-MI LV remodeling, and suggests additional effects over guideline-recommended therapies.

Semiconductor-based laser particles (LPs) with an exceptionally narrowband spectral emission have been used in biological systems for cell tagging purposes. The fabrication of these LPs typically requires highly specialized lithography and etching equipment and is typically done in a cleanroom environment, hindering the broad adoption of this exciting new technology. Here, using only easily accessible laboratory equipment, we demonstrate a simple layer-by-layer fabrication strategy that overcomes this obstacle. We start from an indium phosphide substrate with multiple epitaxial indium gallium arsenide phosphide layers that are sequentially processed to yield LPs of various compositions and spectral properties. The LPs isolated from each layer are characterized, exhibiting excellent optical properties with a lasing emission full width at half maximum as narrow as

Background: Managing repaired tetralogy of Fallot (TOF) patients is still challenging despite the fact that published studies identified prognostic clinical or imaging data with rather good negative predictive accuracy but weak positive predictive accuracy. Heterogeneity of the initial anatomy, the surgical approach, and the complexity of the mechanism leading to dilation and ventricular dysfunction explain the challenge of predicting the adverse event in this population. Therefore, risk stratification and management of this population remain poorly standardized. Design: The CMR/CT WG of the Italian Pediatric Cardiology Society set up a multicenter observational clinical database of repaired TOF evaluations. This registry will enroll patients retrospectively and prospectively assessed by CMR for clinical indication in many congenital heart diseases (CHD) Italian centers. Data collection in a dedicated platform will include surgical history, clinical data, imaging data, and adverse cardiac events at 6 years of follow-up. Summary: The multicenter repaired TOF clinical database will collect data on patients evaluated by CMR in many CHD centers in Italy. The registry has been set up to allow future research studies in this population to improve clinical/surgical management and risk stratification of this population.

The anticoagulant protein S (PS) binds phospholipids with very high affinity, but PS interaction with lipoproteins and lipidrich atherosclerotic plaques remains still poorly defined. We investigated PS in plasma lipoproteins and in atherosclerotic plaques from ten patients undergoing endarterectomy. PS was detected by Western blotting after exposure of the necrotic core to liposomes and was found to maintain its ability to bind phosphatidylserine micelles. The amounts of PS bound to low/very low-density lipoproteins in patient’ plasmas were higher and more variable than those detected in healthy subjects. A direct correlation between bound PS and low-density lipoproteins (LDL), plasma levels was found only in patients (r=0.921, p

Abstract Background We compared cardiovascular magnetic resonance segmental native T1 against T2* values for the detection of myocardial iron overload (MIO) in thalassaemia major and we evaluated the clinical correlates of native T1 measurements. Methods We considered 146 patients (87 females, 38.7 ± 11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassaemia Network. T1 and T2* values were obtained in the 16 left ventricular (LV) segments. LV function parameters were quantified by cine images. Post-contrast late gadolinium enhancement (LGE) and T1 images were acquired. Results 64.1% of segments had normal T2* and T1 values while 10.1% had pathologic T2* and T1 values. In 526 (23.0%) segments, there was a pathologic T1 and a normal T2* value while 65 (2.8%) segments had a pathologic T2* value but a normal T1 and an extracellular volume (ECV) ≥ 25% was detected in 16 of 19 segments where ECV was quantified. Global native T1 was independent from gender or LV function but decreased with increasing age. Patients with replacement myocardial fibrosis had significantly lower native global T1. Patients with cardiac complications had significantly lower native global T1. Conclusions The combined use of both segmental native T1 and T2* values could improve the sensitivity for detecting MIO. Native T1 is associated with cardiac complications in thalassaemia major.

BackgroundLeft ventricular (LV) remodeling consists in maladaptive changes in cardiac geometry and function following an insult such as ST-segment elevation myocardial infarction (STEMI). Interventions able to prevent LV remodeling after a STEMI are expected to improve the outcome of this condition. Paroxetine has inhibitory effects on GRK2, also known as beta-adrenergic receptor kinase 1 (ADRBK1). This drug does not yield beneficial effects on LV remodeling in patients with STEMI and LV ejection fraction ≤ 45%.MethodsWe compared the molecular effects of paroxetine and drugs for neurohormonal antagonism (beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists), using a bioinformatic approach integrating transcriptomic data in a swine model of post-MI and available evidence from the literature and massive public databases.ResultsAmong standard therapies for MI, beta-blockers are the only ones acting directly upon GKR2, but the mechanism of action overlaps with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with respect to the AT2R-mediated anti-hypertensive response. Moreover, beta-blockers could have anti-fibrotic and anti-inflammatory effects through the regulation of myocyte-specific enhancer factors, endothelins and chemokines.ConclusionThe additive benefit of paroxetine on the background of the standard therapy for STEMI, which includes beta-blockers, is expected to be limited. Nonetheless, paroxetine becomes particularly interesting when a beta-blocker is contraindicated (for example, in hypotensive individuals) or poorly tolerated.

Abstract The ability to track individual cells in space over time is crucial to analyzing heterogeneous cell populations. Recently, microlaser particles have emerged as unique optical probes for massively multiplexed single-cell tagging. However, the microlaser far-field emission is inherently direction-dependent, which causes strong intensity fluctuations when the orientation of the particle varies randomly inside cells. Here, we demonstrate a general solution based on the incorporation of nanoscale light scatterers into microlasers. Two schemes are developed by introducing either boundary defects or a scattering layer into microdisk lasers. The resulting laser output is omnidirectional, with the minimum-to-maximum ratio of the angle-dependent intensity improving from 0.007 (−24 dB) to > 0.23 (−6 dB). After transfer into live cells in vitro, the omnidirectional laser particles within moving cells could be tracked continuously with high signal-to-noise ratios for 2 h, while conventional microlasers exhibited frequent signal loss causing tracking failure.

Abstract Background Cardiovascular magnetic resonance (CMR) is part of the diagnostic work-up for cardiac amyloidosis (CA). Deep learning (DL) is an application of artificial intelligence that may allow to automatically analyze CMR findings and establish the likelihood of CA. Methods 1.5 T CMR was performed in 206 subjects with suspected CA (n = 100, 49% with unexplained left ventricular (LV) hypertrophy; n = 106, 51% with blood dyscrasia and suspected light-chain amyloidosis). Patients were randomly assigned to the training (n = 134, 65%), validation (n = 30, 15%), and testing subgroups (n = 42, 20%). Short axis, 2-chamber, 4-chamber late gadolinium enhancement (LGE) images were evaluated by 3 networks (DL algorithms). The tags “amyloidosis present” or “absent” were attributed when the average probability of CA from the 3 networks was ≥ 50% or

IntroductionApolipoprotein C-III (Apo CIII) is a crucial regulator of triglyceride-rich lipoproteins (TRLs) and influences the risk of cardiovascular diseases. High levels of Apo CIII have been also associated with cerebrovascular events and earlier works showed procoagulant effects of Apo CIII. The main aim was to assess whether the plasma concentration of Apo CIII could confer an increased risk of cerebral ischemic events in anticoagulated patients at high-risk of cardioembolism.MethodsWe systematically checked medical records and quantified cerebral ischemic events in a selected cohort of 118 subjects [median age 68 with interquartile range (IQR) 59–75 years, 66.9% males, 52.5% with coronary artery disease (CAD)], taking anticoagulant therapy with warfarin because of atrial fibrillation (AF) and/or mechanical prosthetic heart valves. All the subjects, enrolled between May 1999 and December 2006, were prospectively followed until death or July 31, 2018. Assessments of complete plasma lipid and apolipoprotein profiles, including Apo A-I, B, CIII, and E, were available for all subjects at enrollment.ResultsAfter a median follow-up of 109 months (IQR, 58–187), 24 subjects (20.3%) had cerebral ischemic events: stroke (n = 15) and TIA (n = 9). Subjects with plasma concentration of Apo CIII above the median value (10.3 mg/dL) had an about three-fold increased risk of stroke/TIA than those with lower levels of Apo C-III [hazard ratio 3.08 (95%CI, 1.22–7.77)]. This result was confirmed in multiple Cox regression models adjusted for gender, age, CAD, AF, diabetes, hypertension, plasma lipids, and CHA2DS2-VASc score. By stratifying the sample on the basis of Apo CIII level and CHA2DS2-VASc score, an additive effect was observed with the highest risk in subjects with both high Apo C-III concentration and CHA2DS2-VASc score.ConclusionHigh Apo CIII plasma levels may be associated with an increased risk of ischemic stroke/TIA in high-risk cardiovascular patients anticoagulated with warfarin.

Le questioni che pone l’Agenda 2030 sono orientate sulle tematiche di sostenibilità e resilienza, delineando prospettive e strategie d’azione da intraprendere per un impegno condiviso della società civile nella dimensione allargata della città e dei territori. Questo contributo parte da una rinnovata necessità di ricostruire una nuova forma di organizzazione spaziale e funzionale partendo dalle esperienze svolte nell’ambito della Terza Missione del Politecnico di Bari, per orientare un public engagement verso la promozione di una nuova immagine di città, di paesaggio e di agricoltura, avviando percorsi condivisi verso una transizione ecologica.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19), in which coagulation abnormalities and endothelial dysfunction play a key pathogenic role. Tissue factor (TF) expression is triggered by endothelial dysfunction. Activated factor VII-antithrombin (FVIIa-AT) complex reflects indirectly FVIIa-TF interaction and has been proposed as a potential biomarker of prothrombotic diathesis. FVIIa-AT plasma concentration was measured in 40 patients (30 males and 10 females; 64.8 ± 12.3 years) admitted with SARS-CoV-2 pneumonia during the first pandemic wave in Italy. Two sex- and age-matched cohorts without COVID-19, with or without signs of systemic inflammation, were used to compare FVIIa-AT data. The FVIIa-AT plasma levels in COVID-19 patients were higher than those in non-COVID-19 subjects, either with or without inflammation, while no difference was observed among non-COVID-19 subjects. The association between COVID-19 and FVIIa-AT levels remained significant after adjustment for sex, age, C-reactive protein, renal function, fibrinogen, prothrombin time and activated partial thromboplastin time. Our results indicate that SARS-CoV-2 infection, at least during the first pandemic wave, was characterized by high FVIIa-AT levels, which may suggest an enhanced FVIIa-TF interaction in COVID-19, potentially consistent with SARS-CoV-2-induced endotheliopathy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation mainly affecting the joints leading to cartilage and bone destruction. The definition of seropositive or seronegative RA is based on the presence or absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs). Other autoantibodies have been identified in the last decade such as antibodies directed against carbamylated antigens, peptidyl-arginine deiminase type 4 and v-Raf murine sarcoma viral oncogene homologue B. In order to identify relevant autoantigens, we screened a random peptide library (RPL) with pooled IgGs obtained from 50 patients with seronegative RA. Patients’ sera were then used in an ELISA test to identify the most frequently recognized peptide among those obtained by screening the RPL. Sera from age- and sex-matched healthy subjects were used as controls. We identified a specific peptide (RA-peptide) recognized by RA patients’ sera, but not by healthy subjects or by patients with other immune-mediated diseases. The majority of sera from seronegative and seropositive RA patients (73.8% and 63.6% respectively) contained IgG antibodies directed against the RA-peptide. Interestingly, this peptide shares homology with some self-antigens, such as Protein-tyrosine kinase 2 beta, B cell scaffold protein, Liprin-alfa1 and Cytotoxic T lymphocyte protein 4. Affinity purified anti-RA-peptide antibodies were able to cross react with these autoantigens. In conclusion, we identified a peptide that is recognized by seropositive and, most importantly, by seronegative RA patients’ sera, but not by healthy subjects, conferring to this epitope a high degree of specificity. This peptide shares also homology with other autoantigens which can be recognized by autoantibodies present in seronegative RA sera. These newly identified autoantibodies, although present also in a percentage of seropositive RA patients, may be considered as novel serum biomarkers for seronegative RA, which lacks the presence of RF and/or ACPAs.

ObjectiveApparent mineralocorticoid excess (AME) is an autosomal recessive disorder caused by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme deficiency, traditionally assessed by measuring either the urinary cortisol metabolites ratio (tetrahydrocortisol+allotetrahydrocortisol/tetrahydrocortisone, THF+5αTHF/THE) or the urinary cortisol/cortisone (F/E) ratio. Exosomal mRNA is an emerging diagnostic tool due to its stability in body fluids and its biological regulatory function. It is unknown whether urinary exosomal HSD11B2 mRNA is related to steroid ratio or the HSD11B2 662 C>G genotype (corresponding to a 221 A>G substitution) in patients with AME and essential hypertension (EH).Aim of the StudyTo detect and quantify HSD11B2 mRNA from urinary exosomes in samples from family members affected by AME and EH, and to evaluate the relationship between exosomal HSD11B2 mRNA, steroid ratio, 662C>G genotype, and hypertension.MethodsIn this observational case–control study, urinary steroid ratios and biochemical parameters were measured. Urinary exosomes were extracted from urine and exosomal HSD11B2 mRNA was quantified by Droplet Digital PCR (ddPCR). B2M (β-2 microglobulin) gene was selected as the reference housekeeping gene.ResultsAmong family members affected by AME, exosomal urinary HSD11B2 mRNA expression was strictly related to genotypes. The two homozygous mutant probands showed the highest HSD11B2 mRNA levels (median 169, range 118–220 copies/µl) that progressively decreased in 221 AG heterozygous with hypertension (108, range 92–124 copies/µl), 221 AG heterozygous normotensives (23.35, range 8–38.7 copies/µl), and wild-type 221 AA subjects (5.5, range 4.5–14 copies/µl). Heterozygous hypertensive subjects had more HSD11B2 mRNA than heterozygous normotensive subjects. The F/E urinary ratio correlated with HSD11B2 mRNA copy number (p < 0.05); HSD11B2 mRNA strongly decreased while THF+5αTHF/THE increased in the two probands after therapy. In the AME family, HSD11B2 copy number correlated with both F/E and THF+5αTHF/THE ratios, whereas in EH patients, a high F/E ratio reflected a reduced HSD11B2 mRNA expression.ConclusionsHSD11B2 mRNA is detectable and quantifiable in urinary exosomes; its expression varies according to the 662 C>G genotype with the highest levels in homozygous mutant subjects. The HSD11B2 mRNA overexpression in AME could be due to a compensatory mechanism of the enzyme impairment. Exosomal mRNA is a useful tool to investigate HSD11B2 dysregulation in hypertension.

This report describes a case of a young lady who, following extracardiac bypass between ascending and descending aorta for severe aortic coarctation, underwent 4-dimensional flow cardiac magnetic resonance, a technique that, by 3-dimensional flow assessment over time (4-dimensional), allows not only quantification of flows but also wall shear stress. In this case, increased wall shear stress was observed in the conduit's acute angle (kinking) as well as at the distal anastomosis level. The authors postulate that increased wall shear stress could help identify and risk stratify adult congenital heart disease who could develop vascular complications in the future. (Level of Difficulty: Intermediate.)

Soil texture is key information in agriculture for improving soil knowledge and crop performance, so the accurate mapping of this crucial feature is imperative for rationally planning cultivations and for targeting interventions. We studied the relationship between radioelements and soil texture in the Mezzano Lowland (Italy), a 189 km2 agricultural plain investigated through a dedicated airborne gamma-ray spectroscopy survey. The K and Th abundances were used to retrieve the clay and sand content by means of a multi-approach method. Linear (simple and multiple) and non-linear (machine learning algorithms with deep neural networks) predictive models were trained and tested adopting a 1:50,000 scale soil texture map. The comparison of these approaches highlighted that the non-linear model introduces significant improvements in the prediction of soil texture fractions. The predicted maps of the clay and of the sand content were compared with the regional soil maps. Although the macro-structures were equally present, the airborne gamma-ray data permits us shedding light on finer features. Map areas with higher clay content were coincident with paleo-channels crossing the Mezzano Lowland in Etruscan and Roman periods, confirmed by the hydrographic setting of historical maps and by the geo-morphological features of the study area.

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.

Background White blood cell count, which is inexpensive and widely available in clinical practice, has been proposed to provide prognostic information in coronary artery disease (CAD). Elevated levels of white blood cell subtypes may play different roles in atherothrombosis and predict cardiovascular outcomes. Methods and Results The association between white blood cell counts and mortality was evaluated in 823 subjects with angiographically demonstrated and clinically stable CAD in an observational–longitudinal study. The correlation among white blood cell counts and factor II plasma coagulant activity was analyzed in 750 subjects (554 CAD and 196 CAD‐free) not taking anticoagulant drugs. Subjects with overt leukocytosis or leukopenia were excluded. In the longitudinal study after a median follow‐up of 61 months, 160 (19.4%) subjects died, 107 (13.0%) of whom from cardiovascular causes. High levels of neutrophils, monocytes, eosinophils, and basophils were associated with an increased mortality rate. In multiadjusted Cox regression models, only neutrophils and basophils remained predictors of total and cardiovascular mortality. The associations remained significant after adjustment for traditional cardiovascular risk factors and by including D‐dimer and the chemokine CXCL12 in the regression models. Neutrophils and basophils were also significant predictors of factor II plasma coagulant activity variability after adjustment for blood cell counts, age, sex, inflammatory markers, CAD diagnosis, and prothrombin G20210A polymorphism. Factor II plasma coagulant activity was similarly increased in subjects with high neutrophil and basophil counts and in carriers of the prothrombin 20210A allele. Conclusions Both high neutrophil and basophil blood counts may predict mortality in patients with clinically stable CAD and are associated with enhanced factor II plasma coagulant activity, thereby suggesting underlying prothrombotic mechanisms.

Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories.Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions.After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site.Our analysis demonstrated a high repeatability (CVs 0.7–1.3% for T1, 2.0–7.8% for T2, 1.4–2.5% for normalized PD) and reproducibility (CVs of 2.0–5.8% for T1, 7.4–10.2% for T2, 5.2–9.2% for normalized PD) in gray and white matter.Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.

BackgroundMechanisms underlying hepatocellular carcinoma (HCC) development are largely unknown. The role of trace elements and proteins regulating metal ions homeostasis, i.e. metallothioneins (MTs), recently gained an increased interest. Object of the study was to investigate the role of promoter DNA methylation in MTs transcriptional regulation and the possible prognostic significance of serum trace elements in HCC.MethodsForty-nine HCC patients were enrolled and clinically characterized. Cu, Se, and Zn contents were measured by Inductively Coupled Plasma Mass Spectrometry in the serum and, for a subset of 27 patients, in HCC and homologous non-neoplastic liver (N) tissues. MT1G and MT1H gene expression in hepatic tissues was assessed by Real-Time RT-PCR and the specific promoter DNA methylation by Bisulfite-Amplicon Sequencing.ResultsPatients with Cu serum concentration above the 80th percentile had a significantly decreased survival rate (P < 0.001) with a marked increased hazard ratio for mortality (HR 6.88 with 95% CI 2.60–18.23, P < 0.001). Se and Zn levels were significantly lower in HCC as compared to N tissues (P

A Correction to this paper has been published: https://doi.org/10.1038/s41377-021-00481-1

Abstract Background Salmonella enterica serovar Choleraesuis (S. Choleraesuis) infection causes a systemic disease in pigs. Vaccination could represent a solution to reduce prevalence in farms. In this study, we aimed to assess the efficacy of an attenuated strain of Salmonella enterica serovar Typhimurium (S. Typhimurium ΔznuABC) against S. Choleraesuis infection. The vaccination protocol combined priming with attenuated S. Typhimurium ΔznuABC vaccine and boost with an inactivated S. Choleraesuis vaccine and we compared the protection conferred to that induced by an inactivated S. Choleraesuis vaccine. Methods The first group of piglets was orally vaccinated with S. Typhimurium ΔznuABC and boosted with inactivated S. Choleraesuis, the second one was intramuscularly vaccinated with S. Choleraesuis inactivated vaccine and the third group of piglets was unvaccinated. All groups of animals were challenged with a virulent S. Choleraesuis strain at day 35 post vaccination. Results The results showed that the vaccination protocol, priming with S. Typhimurium ΔznuABC and boosted with inactivated S. Choleraesuis, applied to group A was able to limit weight loss, fever and organs colonization, arising from infection with virulent S. Choleraesuis, more effectively, than the prime-boost vaccination with homologous S. Choleraesuis inactivated vaccine (group B). Conclusion In conclusion, these research findings extend the validity of attenuated S. Typhimurium ΔznuABC strain as a useful mucosal vaccine against S. Typhimurium and S. Choleraesuis pig infection. The development of combined vaccination protocols can have a diffuse administration in field conditions because animals are generally infected with different concomitant serovars.

Sickle cell disease is an autosomal recessive genetic red cell disorder with a worldwide distribution. Growing evidence suggests a possible involvement of complement activation in the severity of clinical complications of sickle cell disease. In this study we found activation of the alternative complement pathway with microvascular deposition of C5b-9 on skin biopsies from patients with sickle cell disease. There was also deposition of C3b on sickle red cell membranes, which is promoted locally by the exposure of phosphatidylserine. In addition, we showed for the first time a peculiar “stop-and-go” motion of sickle cell red blood cells on tumor factor-α–activated vascular endothelial surfaces. Using the C3b/iC3b binding plasma protein factor Has an inhibitor of C3b cell-cell interactions, we found that factor H and its domains 19-20 prevent the adhesion of sickle red cells to the endothelium, normalizing speed transition times of red cells. We documented that factor H acts by preventing the adhesion of sickle red cells to P-selectin and/or the Mac-1 receptor (CD11b/CD18), supporting the activation of the alternative pathway of complement as an additional mechanism in the pathogenesis of acute sickle cell related vaso-occlusive crises. Our data provide a rationale for further investigation of the potential contribution of factor H and other modulators of the alternative complement pathway with potential implications for the treatment of sickle cell disease.

The CO2 fluxes measured by the eddy covariance technique (EC) are presented for a district of the urban area of Bari (Italy). The applicability of the EC method was satisfied even though the measurements were taken at a limited height. The CO2 fluxes are representative of an area with public offices and schools, the university campus, green areas, and busy roads with intensive traffic during school and office times. The measurements were carried out in March–June, covering late winter, characterized by huge vehicle traffic and domestic heating, until late spring, characterized by reduced activities for schools and the university. The source area was determined as a function of atmospheric stability, for data with the ratio between measurement-height/buildings-height in the range of 1.3–1.5. The measured CO2 fluxes were compared to gas consumption values. The results show that the district is a strong source of CO2 during the winter. Emissions were drastically reduced (−82%) after the heating was switched off, and a further decrease in CO2 emissions (−50%) occurred with the reduction of school activities, partly due to the mitigating effect of green areas with large trees in the area.

Ruminants play a crucial role in the food chain, but are also considered contributors of greenhouse gas (GHG) emissions . Essential oils (EOs) are emerging as natural feed additives in ruminants’ nutrition to enhance animal health, performance and reduce environmental footprint. Among EOs, lemongrass (Cymbopogon winterianus) and oregano (Origanum vulgare) EOs (LEO and OEO) have attracted attention as modulators of ruminal fermentations, but their role needs to be clarified. The experiment was designed using a randomised setup to assess the effects of LEO and OEO on in vitro ruminal fermentation and GHGs, using total mixed ration (TMR) as substrate (incubation time 24h). Experimental treatments included (doses as % of TMR on DM basis): 1) control only TMR (0% EOs) 2) 0.07% LEO 3) 0.07% OEO 4) 0.035% LEO + 0.035% OEO 5) 0.07% LEO + 0.07% OEO. Each treatment was repeated three times in two experimental runs. Only EO combinations reduced total gas (−9%, p=0.001). All EOs decreased CO2 emissions by −5 to −12% with no significant differences between treatments (p

Background Apolipoprotein CIII (apo CIII) is a crucial player in triglyceride‐rich lipoprotein metabolism, but may also act pleiotropically, provoking inflammatory responses and stimulating coagulation. Elevated apoCIII plasma levels have been associated with increased activity of coagulation factors. Since these features of prothrombotic diathesis are linked with venous thromboembolism (VTE), we hypothesized that apo CIII plays a role in VTE. Methods and Results We recorded nonfatal VTE events in 1020 patients (age 63.3±11.4 years; 29.1% women) with or without coronary artery disease (79.1% with coronary artery disease and 20.9% without coronary artery disease) during a long follow‐up. Complete plasma lipid and apolipoproteins were available for all patients. Forty‐five patients (4.4%) experienced nonfatal VTE events during a median follow‐up period of 144 months. Apo CIII plasma concentration at enrollment was higher in patients with VTE compared with patients without VTE (12.2 [95% CI, 11.10–13.5] mg/dL vs 10.6 [95% CI, 10.4–10.9] mg/dL, respectively; P=0.011). Patients with apo CIII levels above the median value (10.6 mg/dL) exhibited an increased risk of VTE (incidence rate, 6.0 [95% CI, 4.0–8.0] vs 1.8 [95% CI, 0.7–2.9] VTE events/1000 person‐years; unadjusted hazard ratio [HR], 3.42 [95% CI, 1.73–6.75]; P