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Background Cardiovascular magnetic resonance (CMR) strain imaging is an established technique to quantify myocardial deformation. However, to what extent left ventricular (LV) systolic strain, and therefore LV mechanics, reflects classical hemodynamic parameters under various inotropic states is still not completely clear. Therefore, the aim of this study was to investigate the correlation of LV global strain parameters measured via CMR feature tracking (CMR-FT, based on conventional cine balanced steady state free precession (bSSFP) images) with hemodynamic parameters such as cardiac index (CI), cardiac power output (CPO) and end-systolic elastance (Ees) under various inotropic states. Methods  Ten anaesthetized, healthy Landrace swine were acutely instrumented closed-chest and transported to the CMR facility for measurements. After baseline measurements, two steps were performed: (1) dobutamine-stress (Dobutamine) and (2) verapamil-induced cardiovascular depression (Verapamil). During each protocol, CMR images were acquired in the short axisand apical 2Ch, 3Ch and 4Ch views. MEDIS software was utilized to analyze global longitudinal (GLS), global circumferential (GCS), and global radial strain (GRS). Results Dobutamine significantly increased heart rate, CI, CPO and Ees, while Verapamil decreased them. Absolute values of GLS, GCS and GRS accordingly increased during Dobutamine infusion, while GLS and GCS decreased during Verapamil. Linear regression analysis showed a moderate correlation between GLS, GCS and LV hemodynamic parameters, while GRS correlated poorly. Indexing global strain parameters for indirect measures of afterload, such as mean aortic pressure or wall stress, significantly improved these correlations, with GLS indexed for wall stress reflecting LV contractility as the clinically widespread LV ejection fraction. Conclusion GLS and GCS correlate accordingly with LV hemodynamics under various inotropic states in swine. Indexing strain parameters for indirect measures of afterload substantially improves this correlation, with GLS being as good as LV ejection fraction in reflecting LV contractility. CMR-FT-strain imaging may be a quick and promising tool to characterize LV hemodynamics in patients with varying degrees of LV dysfunction.

Right ventricular biopsy represents the gold standard for the assessment of myocardial fibrosis and collagen content. This invasive technique, however, is accompanied by perioperative complications and poor reproducibility. Extracellular volume (ECV) measured through cardiovascular magnetic resonance (CMR) has emerged as a valid surrogate method to assess fibrosis non-invasively. Nonetheless, ECV provides an overestimation of collagen concentration since it also considers interstitial space. Our study aims to investigate the feasibility of estimating total collagen volume (TCV) through CMR by comparing it with the TCV measured at histology. Seven healthy Landrace pigs were acutely instrumented closed-chest and transported to the MRI facility for measurements. For each protocol, CMR imaging at 3T was acquired. MEDIS software was used to analyze T1 mapping and ECV for both the left ventricular myocardium (LVmyo) and left ventricular septum (LVseptum). ECV was then used to estimate TCVCMR at LVmyo and LVseptum following previously published formulas. Tissues were prepared following an established protocol and stained with picrosirius red to analyze the TCVhisto in LVmyo and LVseptum. TCV measured at LVmyo and LVseptum with both histology (8 ± 5 ml and 7 ± 3 ml, respectively) and T1-Mapping (9 ± 5 ml and 8 ± 6 ml, respectively) did not show any regional differences. TCVhisto and TCVCMR showed a good level of data agreement by Bland–Altman analysis. Estimation of TCV through CMR may be a promising way to non-invasively assess myocardial collagen content and may be useful to track disease progression or treatment response.

4D-flow MRI is a promising technique for assessing vessel hemodynamics. However, its utilization is currently limited by the lack of reference values, particularly for pulmonary vessels. In this work, we have analysed flow and velocity in the pulmonary trunk (PT), left and right pulmonary arteries (LPA and RPA, respectively) in Landrace pigs at both rest and stress through the software MEVISFlow. Nine healthy Landrace pigs were acutely instrumented closed-chest and transported to the CMR facility for evaluation. After rest measurements, dobutamine was administered to achieve a 25% increase in heart rate compared to rest. 4D-flow MRI images have been analysed through MEVISFlow by two independent observers. Inter- and intra-observer reproducibility was quantified using intraclass correlation coefficient. A significant difference between rest and stress regarding flow and velocity in all the pulmonary vessels was observed. Mean flow increased 55% in PT, 75% in LPA and 40% in RPA. Mean peak velocity increased 55% in PT, 75% in LPA and 66% in RPA. A good-to-excellent reproducibility was observed in rest and stress for flow measurements in all three arteries. An excellent reproducibility for velocity was found in PT at rest and stress, a good one for LPA and RPA at rest, while poor reproducibility was found at stress. The current study showed that pulmonary flow and velocity assessed through 4D-flow MRI follow the physiological alterations during cardiac cycle and after stress induced by dobutamine. A clinical translation to assess pulmonary diseases with 4D-flow MRI under stress conditions needs investigation.

Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel technique for non-invasive assessment of myocardial motion and deformation. Although CMR-FT is standardized in humans, literature on comparative analysis from animal models is scarce. In this study, we measured the reproducibility of global strain under various inotropic states and the sample size needed to test its relative changes in pigs. Ten anesthetized healthy Landrace pigs were investigated. After baseline (BL), two further steps were performed: (I) dobutamine-induced hyper-contractility (Dob) and (II) verapamil-induced hypocontractility (Ver). Global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were assessed. This study shows a good to excellent inter- and intra-observer reproducibility of CMR-FT in pigs under various inotropic states. The highest inter-observer reproducibility was observed for GLS at both BL (ICC 0.88) and Ver (ICC 0.79). According to the sample size calculation for GLS, a small number of animals could be used for future trials.

ObjectivesImplants are used to replace congenitally missing lateral incisors but often the space across the alveolar crest is too narrow to permit their use. This multicenter study (Dental Clinic of the University of Foggia, Odontostomatology Clinic of the University of L’Aquila) evaluated the efficacy of mini-implants in cases of maxillary lateral incisor agenesis with severe osseous atrophy in 10-year follow-up.Materials and methodsForty-seven mini-implants have been inserted in 35 patients affected by lateral incisors agenesis (23 single and 12 bilateral ageneses). All patients underwent orthodontic opening of the space of the upper lateral incisors. After the insertion of the implants, the immediate, non-functional loading, positioning of crowns, presence of pain during percussion and mini-implant function, horizontal and vertical movement when a force of 5 N was applied, ridge loss, and plaque index have been evaluated 1 month after loading, 1 year after loading, and then every 5 years in the following 10 years. Little’s test was used to evaluate the assumption that data of loss to follow-up implants are missing completely at random (MCAR) and that a complete-case scenario could be adopted. Wilcoxon test was carried out to look statistically significant differences between the various parameters resulting in the complete-case scenario and those assumed for the worst scenario. The software R (v. 3.6.1, 2019) was employed to perform the statistical analysis.ResultsThe results obtained over 10 years range from 89% of success rate in a worst-case scenario to the 100% using a complete-case analysis with satisfactory values of marginal bone resorption and good conditions of the peri-implant tissue. Ten-year follow-up using complete-case analysis shows survival rates of 100% for implants with no signs of peri-implantitis, stability of the marginal bone levels and soft tissue around the dental implants.ConclusionsThe data collected show very good implant stability, absence of progressive peri-implantitis, and satisfactory aesthetical results in time (no signs of infraocclusion).Clinical relevanceMini-implants can be considered a valid and stable over time solution in the restorative treatment of maxillary lateral incisors agenesis.

Bone resorption in edentulous regions often results in inadequate ridge for implant osseointegration. In order to overcome this problem, the use of osteoconductive biomaterials has been proposed as a carrier for different types of pharmacological molecules. Since raloxifene, a drug used in osteoporosis therapy, inhibits the osteoclast, but not osteoblast functions, it has been suggested to improve recovery during implant surgery. The present work evaluated in vitro the effect of raloxifene on two different cell populations: the human osteoblast-like cells (MG63) and osteoblasts derived from rat calvaria (MC3T3-E1). The morpho-functional investigations carried out showed a different behavior of the two cell lines. Raloxifene showed a stimulatory effect towards MG63 cell proliferation with a significant increase in cell viability after 7 days of culture. On the contrary, MC3T3-E1 cells showed a significant reduction in cell viability, when compared with the same cells at 72 h, or with the control cell population. The predominantly proliferative effect of raloxifene on MG63 cells is partly confirmed by the reduction of alkaline phosphatase activity, an early marker of osteoblast differentiation. The different effect of raloxifene on osteoblastic population in relationship to the type and age of the cell is an issue that needs further investigation.

Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and/or in the expression of oncoproteins and tumor suppressor genes. For this reason, formalin-fixed paraffin-embedded sections of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin Dl) onco-proteins. Most of the epithelial lining of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome showed nuclear immunopositivity for p53 protein and overexpression of cyclin Dl with various degrees of staining intensity. All sporadic odontogenic keratocysts were negative for p53 and cyclin Dl. The expressions of bcl-2 oncoprotein were found to be substantially similar between the two groups of lesions, with a cytoplasmic immunopositivity localized only in the resting reserve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, the finding of cyclin Dl and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin Dl and p53 proteins, involved in a check-point control of cellular proliferation.

Saliva is a non-invasive medium, its analysis is useful to measure a wide range of hormones, drugs, narcotics, antibodies, host, microbial, fungal and viral DNA up to salivary mRNA; hence, it has been suggested to be an easy and reliable biomarker in disease diagnostics, such as inflammatory mouth infections/diseases, and in normal health surveillance. In light of this potential, our primary endpoint is to review the current knowledge on saliva analyses and its recent methods of sampling.

Sleep disturbance (SD) and mood disorders (MD) are common among Burning Mouth Syndrome (BMS) patients. The aim of this study was to investigate sleep complaints in a large cohort of Italian patients with BMS and the relationships between these disturbances, negative mood and pain. There are 200 patients with BMS versus an equal number of age and sex-matched healthy controls, recruited in 10 centers, were enrolled. The study was based on the statistical evaluation of questionnaires examining insomnia symptoms and excessive daytime sleepiness (Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale), depression and anxiety (the Hamilton rating scale for depression and the Hamilton rating scale for anxiety) and pain (Numeric Pain Intensity Scale and Short Form of Mc Gill Pain Questionnaire). The BMS patients reported a greater degree of sleep disorders, anxiety, and depression as compared with the controls, highlighting the interrelation between sleep and mood. Sleep disturbance could influence the quality of life of BMS patients and could be a possible treatment target.