4D flow MRI: impact of region of interest size, angulation and spatial resolution on aortic flow assessment.

Objectives.In cardiovascular magnetic resonance, the 3D time-resolved phase-contrast technique, also known as 4D flow, is gaining increasing attention due to applications that exploit three-directional velocity encoding throughout the cardiac cycle. Blood flow volume assessment usually requires an expert to draw regions of interest (ROI) around the vessel cross section, whereas the errors involved in this estimation have not been thoroughly investigated. Our objective is to quantify the influence of ROI sizing, angulation and spatial resolution of the reconstructed plane employed in blood flow measurements using 4D flow.Approach.Three circular ROIs were drawn around the ascending, arch and descending aorta of healthy volunteers (n= 27) and patients with a dilated ascending aorta or bicuspid valve (n= 37). We applied systematic changes of ROI diameter (up to ±10%), tilt angle (up to ±25°) and spatial resolution (from 0.25 to 2 mm) of the reconstructed oblique planes, calculating the effects on net, forward and backward blood flow volumes.Main results.Patients had a larger ascending aorta than healthy volunteers with similar ages and male sex proportion (60 ± 15 y.o. vs 58 ± 16 y.o. and 84% vs 70%, respectively). Higher forward and backward flow volumes were observed in the ascending aorta and the aortic arch of the patients with respect to controls (p< 0.001), whereas net volumes were similar: 74.0 ± 20.8 ml versus 75.7 ± 21.8 ml (p= 0.37), respectively. The ascending aorta was the most sensitive to ROI modifications. Changes of ±10% in the ROI diameter and ±25° in tilt angles produced flow volume differences of up to 9 ml (10%) and 18 ml (15%) in controls and patients, respectively. Modifying the reconstructed planes spatial resolution produced flow volume changes below 2 ml.Significance.Since the setting of the ROI size and plane angle could produce errors that represent up to 20% of the forward and/or backward aortic flow volume, a good standardization for vessel segmentation and plane positioning is desirable.

Microbiota and microRNAs in lung diseases: mutual influence and role insights.

Trillions of microbial cells colonize human body both internally and externally. The prevalent amount of these reside in the gastrointestinal tract (gut microbiome). Gut microflora support the transformation of food nutrients. The products of this modification processes both modulate gastro-intestinal immunity, and influence other organs such as lung and brain. Recently, it was reported the role of micro-RNAs (miRNAs) as regulators in different pathways of the innate and/or adaptive immune responses. Latest studies discussed the aptitude of probiotics strains to balance the host immune response at a post-transcriptional level by controlling miRNAs expression. We speculated a model of lung immune regulation driven by the axis microbiota-microRNAs, involving asthma, acute injury, cancer and COPD. Based on this axis, we propose a novel approach based on the modification of microRNAs expression centered not exclusively on antagomiRs but also on microbiota modification in order to further potentiate their therapeutic effects.

Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: A systematic review.

Familial Mediterranean fever (FMF) is the most common autosomal recessive autoinflammatory disease. To date, following the isolation of more than 280 MEFV sequence variants, the genotype-phenotype correlation in FMF patients has been intensively investigated; however, an univocal and clear consensus has not been yet reached. Thus, the aim of this systematic review was to analyze the available literature findings in order to provide to scientific community an indirect estimation of the impact of genetic factors on the phenotypic variability of FMF. This systematic review has been conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The p.M694V mutation was reported to have a relatively severe clinical course, similarly, patients homozygous for M694I and M680I, or carrying a combination of both at codons 694 and 680, have a severe disease. Also, patients homozygous for M694V and V726A variants experienced more severe clinical picture. Conversely, heterozygous p.V726A and p.E148Q genotypes have been correlated with a milder disease course. At present, doubts remain on the potential pathogenic role of E148Q variant. The heterogenity in clinical FMF manifestations reflects the changes occuring in repertoire of mutations. We believe that clinical criteria and gene tests, enhancing each other, could better support the diagnosis of FMF.

Continuous assessment of carotid intima-media thickness applied to estimate a volumetric compliance using B-mode ultrasound sequences.

Recent reports have shown that the carotid artery wall had significant movements not only in the radial but also in the longitudinal direction during the cardiac cycle. Accordingly, the idea that longitudinal elongations could be systematically neglected for compliance estimations became controversial. Assuming a dynamic change in vessel length, the standard measurement of cross-sectional compliance can be revised. In this work, we propose to estimate a volumetric compliance based on continuous measurements of carotid diameter and intima-media thickness (IMT) from B-mode ultrasound sequences. Assuming the principle of conservation of the mass of wall volume (compressibility equals zero), a temporal longitudinal elongation can be calculated to estimate a volumetric compliance. Moreover, elongations can also be estimated allowing small compressibility factors to model some wall leakage. The cross-sectional and the volumetric compliance were estimated in 45 healthy volunteers and 19 asymptomatic patients. The standard measurement underestimated the volumetric compliance by 25% for young volunteers (p < 0.01) and 17% for patients (p < 0.05). When compressibility factors different from zero were allowed, volunteers and patients reached values of 9% and 4%, respectively. We conclude that a simultaneous assessment of carotid diameter and IMT can be employed to estimate a volumetric compliance incorporating a longitudinal elongation. The cross-sectional compliance, that neglects the change in vessel length, underestimates the volumetric compliance.

Three-dimensional evaluation of thoracic aorta enlargement and unfolding in hypertensive men using non-contrast computed tomography.

Aging produces a simultaneous thoracic aorta (TA) enlargement and unfolding. We sought to analyze the impact of hypertension on these geometric changes. Non-contrast computed tomography images were obtained from coronary artery calcium scans, including the entire aortic arch, in 200 normotensive and 200 hypertensive asymptomatic men. An automated algorithm reconstructed the vessel in three-dimensions, estimating orthogonal aortic sections along the whole TA pathway, and calculated several geometric descriptors to assess TA morphology. Hypertensive patients were older with respect to normotensive (P<0.001). Diameter and volume of TA ascending, arch and descending segments were higher in hypertensive patients with respect to normotensive (P<0.001) and differences persisted after adjustment for age. Hypertension produced an accelerated unfolding effect on TA shape. We found increments in aortic arch width (P<0.001), radius of curvature (P<0.001) and area under the arch curve (P<0.01) with a concomitant tortuosity decrease (P<0.05) and no significant change in aortic arch height. Overall, hypertension produced an equivalent effect of 2-7-years of aging. In multivariate analysis adjusted for age and hypertension treatment, diastolic pressure was more associated to TA size and shape changes than systolic pressure. These data suggest that hypertension accelerates TA enlargement and unfolding deformation with respect to the aging effect.

Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection.

The present study demonstrates that the quality of the virus-specific CD8(+) T cell responses, as detected by both enzyme-linked immunospot assay and specific MHC-peptide tetramers, changed in relation to the different disease activity in chronically hepatitis C virus-infected patients. Indeed, both the serum alanine transaminase and the hepatic flogosis levels were related directly to the frequencies of peripheral memory effector CD8(+) T cells producing IFN-gamma (Tc1), but inversely to the frequencies of those producing both IL-4 and IL-10 (Tc2). Longitudinal studies highlighted that Tc1 or Tc2 responses fluctuate in relation to the different phases of the disease in the same individual. Furthermore, the Tc1 or Tc2 phenotype correlates with tetramer-positive cells expressing either CXCR3 or CCR3, promoting differential tissue localization of these cells and the maintenance of T cell homeostasis. Finally, studies at the level of liver-infiltrating lymphocytes indicated that they produced both IFN-gamma and IL-4 with an evident bias towards the Tc1-like phenotype. Our studies suggest that the progressive fluctuation of Tc1 and Tc2 responses may play a fundamental role in maintaining a long-lasting low-level liver inflammation, and may constitute the basis for new therapeutic strategies of immune regulation.

Presence of effector CD8+ T cells in hepatitis C virus-exposed healthy seronegative donors.

CTL responses against multiple hepatitis C virus (HCV) epitopes were detected in 7 of 29 (24.1%) healthy family members (HFM) persistently exposed to chronically HCV-infected patients (HCV-HFM). These precursor CTL were at very low or undetectable frequencies, as determined by limiting dilution analysis. However, when HCV-specific effector CD8+ T cells, freshly isolated from PBMC of HCV-HFM, were assessed by a sensitive enzyme-linked immunospot assay, their frequencies were severalfold higher than those of precursor CTL. These results indicate that the two assays detect two functionally distinct T cell populations and that the effector cells are not assayed by the 51Cr-release assay. Furthermore, the combination of cell depletion and enzyme-linked immunospot analyses showed that the effector cells were confined into a CD8+ CD45RO+ CD28- population. The persistence of effector CD8+ T cells specific for both the structural and nonstructural viral proteins in uninfected HCV-HFM, suggest that: 1) an immunological memory is established upon a subclinical infection without any evidence of hepatitis, in a large cohort of HCV-exposed individuals; 2) because these cells required neither restimulation nor the addition of particular cytokines in vitro for differentiating in effectors, they should be capable of prompt HCV-specific effector function in vivo, possibly providing antiviral protection; and 3) the maintenance of effector T cell responses may be sustained by persisting low-level stimulation induced by inapparent infections.

Defective Th1 and Th2 cytokine synthesis in the T-T cell presentation model for lack of CD40/CD40 ligand interaction.

In this study, T or NK cell clones used as antigen-presenting cells (T- or NK-APC) were shown to be significantly less efficient than professional APC in inducing Th1 and Th2 cytokines by antigen-specific T cell clones. This phenomenon was not related to a limited engagement of TCR by T-APC, since comparable thresholds of TCR down-regulation were shown when antigen was presented by either T-APC or professional APC. Rather, the stimulatory T-APC weakness was due to their inability, because they are CD40-, to provide the appropriate co-stimuli to responder T cells both indirectly via IL-12, and partially via direct CD40L triggering on T cells. Indeed, the simultaneous addition of IL-12 and reagents directly engaging CD40L on responder T cells restored T cell cytokine synthesis when antigen was presented by T-APC. In addition, either IL-12 production or blocking of T cell cytokine synthesis by anti-IL-12 p75 antibodies was evident only when professional APC were used in our antigen-specific system. The down-regulation of cytokine synthesis in the system of T-T cell presentation could represent a novel mechanism of immune regulation, which may intervene to switch off detrimental Th1- or Th2-mediated responses induced by antigen presentation among activated T cells infiltrating inflamed tissues.

[Juvenile dyslipidemia as early risk factor for atherosclerosis. Analysis of a sample of school age boys]. / Le dislipidemie giovanili come fattore di rischio precoce di aterosclerosi. Analisi di un campione di giovani di sesso maschile in età scolare.

Atherosclerosis appears already in the first years of life. Several factors may accelerate the age of onset and the gravity of its symptoms. Particular importance is attributed to lipid metabolism in youth. Ther Authors studied the rates of cholesterol, HDL, LDL, triglycerides, apolipoproteins AI and B100, lipoprotein a and several anamnestic and anthropometric parameters in a group of 103 young people of Rome, between 16 and 19 years of age. They processed these data statistically and compared them with those of a similar American group. The results showed a tendency to fatness in the Italian sample, and to dyslipidosis in the American group. Besides, the subjects who had been breast-fed presented higher blood levels of cholesterol and apolipoprotein B100.