Three-Dimensional Automated, Machine-Learning-Based Left Heart Chamber Metrics: Associations with Prevalent Vascular Risk Factors and Cardiovascular Diseases

Background. Three-dimensional transthoracic echocardiography (3DE) powered by artificial intelligence provides accurate left chamber quantification in good accordance with cardiac magnetic resonance and has the potential to revolutionize our clinical practice. Aims. To evaluate the association and the independent value of dynamic heart model (DHM)-derived left atrial (LA) and left ventricular (LV) metrics with prevalent vascular risk factors (VRFs) and cardiovascular diseases (CVDs) in a large, unselected population. Materials and Methods. We estimated the association of DHM metrics with VRFs (hypertension, diabetes) and CVDs (atrial fibrillation, stroke, ischemic heart disease, cardiomyopathies, >moderate valvular heart disease/prosthesis), stratified by prevalent disease status: participants without VRFs or CVDs (healthy), with at least one VRFs but without CVDs, and with at least one CVDs. Results. We retrospectively included 1069 subjects (median age 62 [IQR 49–74]; 50.6% women). When comparing VRFs with the healthy, significant difference in maximum and minimum indexed atrial volume (LAVi max and LAVi min), left atrial ejection fraction (LAEF), left ventricular mass/left ventricular end-diastolic volume ratio, and left ventricular global function index (LVGFI) were recorded (p < 0.05). In the adjusted logistic regression, LAVi min, LAEF, LV ejection fraction, and LVGFI showed the most robust association (OR 3.03 [95% CI 2.48–3.70], 0.45 [95% CI 0.39–0.51], 0.28 [95% CI 0.22–0.35], and 0.22 [95% CI 0.16–0.28], respectively, with CVDs. Conclusions. The present data suggested that novel 3DE left heart chamber metrics by DHM such as LAEF, LAVi min, and LVGFI can refine our echocardiographic disease discrimination capacity

Administration of DNA Plasmid Coding Protein Aggregating Domain Induces Inflammatory Bone Loss.

Background: Plasmids coding protein aggregation polypeptides from different sources have beenproposed as genetic adjuvants for DNA vaccines. We reported that a plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A (vWA/A) domain of the Anthrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates and subsequent cell death. Aims: In the present study we addressed the question of whether there is any substantial immunotoxicity associated with the use of self-aggregating proteins as genetic adjuvants. Results: Here we report, by mean of histology, X-ray and molecular examinations of bone specimens, the unexpected finding that intramuscular injection of pATRex in mice triggers, per se, severe bone loss (osteoporosis) independently from the sex and genotype of the treated animals. Conclusion: Even though the study suggests that proteinaceous “sticky “ adjuvants are unlikely to find their way into practical vaccination, the information gained is of value as ATRex injections could provide an additional, simplified, mouse model of osteoporosis. Moreover, our results provide an experimental support to the hypothesis that proteotoxic aggregates chronically activate the innate immune system in amyloid and aggregosome disorders

Quantification of Myocardial Contraction Fraction with Three-Dimensional Automated, Machine-Learning-Based Left-Heart-Chamber Metrics: Diagnostic Utility in Hypertrophic Phenotypes and Normal Ejection Fraction

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA (n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43–67.79%), mean values for MCF were significantly reduced in HCM—48.55% (43.46–54.86% p < 0.001)—and CA—40.92% (36.68–46.84% p < 0.002)—but not in IH—59.35% (53.22–64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R2 = 0.136) and the four study subgroups (healthy adults, R2 = 0.039 IH, R2 = 0.089; HCM, R2 = 0.225; CA, R2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients

Assessment of antioxidant activity of carotenoid-enriched extracts from peach fruits using the new LOX/RNO method

Peach (Prunus persica L.) fruits contain several health-promoting phytochemicals. Among these, carotenoids, in addition to being involved in determining flesh color, play a relevant role in cell protection against oxidative stress. Nevertheless, antioxidant activity (AA) of peach carotenoids so far has not been investigated in as much detail as phenols. In the present study, for the first time, AA of peach carotenoid extracts was evaluated using the innovative lipoxygenase/4-nitroso-N,N-dimethylaniline (LOX/RNO) method, able to simultaneously detect different antioxidant mechanisms and synergistic antioxidant interactions, as well as using the well-known ORAC and TEAC assays. In particular, extracts were obtained from fruits collected in S4 development stage from two yellow-fleshed (Armking and Redhaven) and three white-fleshed (Silverking, Caldesi 2000, IFF331) varieties. The LOX/RNO method gave high AA values (10-150 μmol eq. Trolox/g f.w.), about 85-1900-fold higher than ORAC and TEAC methods. Moreover, the ratio between AA values, measured by the LOX/RNO method, of yellow- and white-fleshed peaches resulted equal to 14, but only 2.6 and 3.6 for ORAC and TEAC, respectively. Results of this study indicate that the LOX/RNO method, measuring high AA values and easily discriminating among samples, is an advisable tool to assess the AA of the carotenoid component in peach