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OBJECTIVE: To understand whether patients with post-ischemic dilated cardiomyopathy and myocardial viability (MV) could benefit from cardiac resynchronization therapy (CRT) in terms of clinical, echocardiographic and neuro- hormonal parameters compared to patients without MV. METHODS: One hundred and four consecutive patients were enrolled in a prospective observational cohort study. Using dobutamine stress echocardiography, 2 groups were identified: group A of 51 patients with MV and group B of 53 patients without MV. All patients were implanted with biventricular pacing devices combined with an internal cardioverter-defibrillator. Clinical, echocardiographic and neuro-hormonal parameters were evaluated at baseline and at six month follow-up. Analysis of variance for repeated measures on each variable suggestive of remodeling was performed. We considered responder every patient with: decrease of > 15% in left ventricular volumes and/or improvement in left ventricular ejection fraction of > 5% in addition to NYHA class improvement. RESULTS: All the variables improved in both groups (time effect). Comparing the two groups (group effect), the following variables were significantly better in group A: N-terminal pro-B-type natriuretic peptide (p=0.02), NYHA class (p=0.003), reverse remodeling (RR) (p=0.007), dP/dt (p=0.005), left ventricular ejection fraction (p=0.009), 3rd sound (p=0.01), and left ventricular end-systolic volume after the first week (p=0.035). RR occurred at the first week after CRT only in Group A and was maintained for all the time of this study. The maximum difference of the decrease of left ventricular volumes between the two groups occurred after the first week (p<0.001). CONCLUSION: Patients with MV responded better than patients without MV with a significant improvement after the first week from CRT. [ABSTRACT FROM AUTHOR]

The products of c-fos and c-jun proto-oncogenes form the heterodimeric complex AP-1 (activator protein 1), which play an important part in the control of bone cell proliferation and differentiation and in the development of bone tumours. We examined the expression of c-fos and c-jun in a series of 52 primary skeletal neoplasms, using an immunohistochemical method on formalin-fixed, paraffin-embedded sections. The expression of c-fos and c-jun was restricted to bone-forming lesions, while cartilaginous tumours were devoid of immunoreactivity. In benign osteoblastic lesions moderate c-fos and c-jun expression was found in 2 cases (18.1%). The highest levels of c-fos and c-jun expression were detected in high-grade central osteosarcomas (7 of 15 cases with moderate/diffuse expression) while 1 telangiectatic osteosarcoma, 2 low-grade central osteosarcomas, 1 low-grade periosteal osteosarcoma and 7 low-grade parosteal osteosarcomas were either negative or had low expression. The high-grade component of a dedifferentiated parosteal osteosarcoma showed diffuse immunoreactivity for both oncoproteins. Comparison of c-fos and c-jun expression by histological grade showed that high-grade osteosarcomas had a significantly higher expression of both oncoproteins than did low-grade osteosarcomas (P = 0.01, Fisher's exact test). Thus, c-fos and c-jun overexpression may be implicated in the development of high-grade osteosarcomas, but they appear to have little or no relevance for the development of low-grade osteosarcomas and cartilaginous skeletal neoplasms. [ABSTRACT FROM AUTHOR]

Idiopathic dilatation of the pulmonary artery (IDPA) is an uncommon anomaly occurring in 0.6% of patients with congenital heart disease. IDPA is characterized by the enlargement of the main pulmonary artery with or without dilatation of the right and left pulmonary arteries. We describe 2D and Real-Time 3D Echocardiography findings in a young adult with IDPA. To the best of our knowledge this is the first case reporting all echocardiographic findings diagnostic for IDPA. [ABSTRACT FROM AUTHOR]

Abstract Background Cardiac allograft vasculopathy (CAV) is a major late complication in cardiac transplant recipients and has a relevant impact on outcome of these patients. Aims of this study: to compare, in cardiac transplant recipients patients, the diagnostic value of pressure/volume relationship (ESPVR) during dobutamine stress echocardiography (DSE) for coronary artery disease, assessed by Multislice Computed Tomography (MSCT), and by coronary angiography (CA). We also analyzed any possible relationship between ESPVR and the Health Related Quality of Life of the patients (HRQoL), evaluated by SF–36 questionnaire. Methods 25 consecutive patients underwent DSE within 24 hours after MSCT coronary angiogram and then they underwent CA. The HRQoL questionnaire was administered to the patients in the settings of DSE. They were followed-up for 6 months. Results DSE has a sensitivity in detecting CAV of 67%, specificity of 95%, positive predictive value of 67% and negative predictive value of 95%; DSE with ESPVR has a sensitivity of 100%, specificity of 95%, positive predictive value of 75%, negative predictive value of 100%; MSCT has a sensitivity of 100%; specificity of 82%; positive predictive value of 43%; negative predictive value of 100%. Htx recipients with a flat-biphasic ESPVR, although asymptomatic, perceived a worst HRQoL compared with the up-sloping ESPVR population, and this is statistically significant for the general health (p 0.0004), the vitality (p 0.0013) and the mental health (p 0.021) SF-36 subscale. Conclusions Evaluation with DSE and ESPVR is accurate in the clinical control of heart transplant recipients reserving invasive evaluation only for patients with abnormal contractility indexes.

Abstract Objectives This study was designed to describe Doppler-echocardiography values of Carpentier-Edwards Perimount Standard (CEPS) and Carpentier-Edwards Perimount Magna (CEPM) aortic prosthetic valves, evaluated by a single, experienced echo-laboratory, early in the postoperative phase. Methods Three-hundred-seventy-seven consecutive patients, who had had a CEPS or a CEPM implanted in our Hospital due to aortic stenosis and/or insufficiency, underwent baseline Doppler echocardiography evaluation within 7 days after surgery. Hemodynamic performances of CEPS and CEPM were accurately described, evaluating flow-dependent (transprosthetic velocities and gradients) and flow-independent (effective orifice area, indexed effective orifice area and Doppler velocity index) Doppler-echocardiography parameters. Results Out of the 377 patients 48.8% were men (n = 184), mean age was 74.63 ± 6.77 years, mean BSA was 1.78 ± 0.18 m2, mean ejection fraction was 57.78 ± 8%. Two-hundred and sixty two CEPS and 115 CEPM were implanted. Comparing size-by-size CEPS with CEPM, both prostheses showed a good hemodynamic profile, with fairly similar values of pressure gradients (PGmax and mean, in mmHg, = 37,18 ± 11.57 and 20.81 ± 7.44 in CEPS n°19 compared to 32,47 ± 7,76 and 17,67 ± 4.63 in CEPM n°19 and progressively lower in higher sized prostheses, having PGmax and mean 15 ± 3,16 and 9.15 ± 1,29 in CEPS n°29 compared to 15,67 ± 1,53 and 9 ± 1 in CEPM n°29) and EOAi (being 0,65 ± 0,33 cm²/m² in CEPS n°19 compared to 0,77 ± 0,29 cm²/m² in CEPM n°19 and progressively higher in higher sized prostheses, being 1,28 ± 0,59 cm²/m² in CEPS n°29 compared to 1,07 ± 0,18 cm²/m² in CEPM n°29), the latter resulting, however, basically less flow obstructive. Conclusions Our data confirm the good hemodynamic performance of both aortic bioprostheses and the more favourable hemodynamic profile of CEPM compared to CEPS, pointing out the need to perform routinely an accurate baseline Doppler-echocardiography evaluation early after surgery to allow an adequate interpretation of data at follow-up.

In a 72-year-old male patient an acute coronary syndrome (ACS) was complicated by left ventricular aneurysm and severe mitral regurgitation. Two-dimensional echocardiography failed in detecting mechanism of mitral regurgitation. Transthoracic three dimensional echocardiography allowed us to obtain a better visualization of the relationship between papillary muscles, ventricular walls and mitral leaflets and dynamic systolic displacement of the posterior papillary muscle associated with restriction of both leaflets with greater apical tethering of anterior leaflet (A3-A2 scallops). Echocardiography performed after cardiac surgery revealed that ventricular reshaping after posterior papillary muscle realignment allowed the mitral regurgitation resolution. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane-enclosed bio-nanoparticles secreted by cells and naturally evolved to transport various bioactive molecules between cells and even organisms. These cellular objects are considered one of the most promising bio-nanovehicles for the delivery of native and exogenous molecular cargo. However, many challenges with state-of-the-art EV-based candidates as drug carriers still exist, including issues with scalability, batch-to-batch reproducibility, and cost-sustainability of the final therapeutic formulation. Microalgal extracellular vesicles, which we named nanoalgosomes, are naturally released by various microalgal species. Here, we evaluate the innate biological properties of nanoalgosomes derived from cultures of the marine microalgae Tetraselmis chuii, using an optimized manufacturing protocol. Our investigation of nanoalgosome biocompatibility in preclinical models includes toxicological analyses, using the invertebrate model organism Caenorhabditis elegans, hematological and immunological evaluations ex vivo and in mice. We evaluate nanoalgosome cellular uptake mechanisms in C. elegans at cellular and subcellular levels, and study their biodistribution in mice with accurate space-time resolution. Further examination highlights the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization demonstrates that they are biocompatible and innate bioactive effectors with unique bone tropism. These findings suggest that nanoalgosomes have significant potential for future therapeutic applications., (© 2024. The Author(s).)

Wilson disease (WD) is caused by mutations in the ATP7B gene that encodes a copper (Cu) transporting ATPase whose trafficking from the Golgi to endo-lysosomal compartments drives sequestration of excess Cu and its further excretion from hepatocytes into the bile. Loss of ATP7B function leads to toxic Cu overload in the liver and subsequently in the brain, causing fatal hepatic and neurological abnormalities. The limitations of existing WD therapies call for the development of new therapeutic approaches, which require an amenable animal model system for screening and validation of drugs and molecular targets. To achieve this objective, we generated a mutant Caenorhabditis elegans strain with a substitution of a conserved histidine (H828Q) in the ATP7B ortholog cua-1 corresponding to the most common ATP7B variant (H1069Q) that causes WD. cua-1 mutant animals exhibited very poor resistance to Cu compared to the wild-type strain. This manifested in a strong delay in larval development, a shorter lifespan, impaired motility, oxidative stress pathway activation, and mitochondrial damage. In addition, morphological analysis revealed several neuronal abnormalities in cua-1 mutant animals exposed to Cu. Further investigation suggested that mutant CUA-1 is retained and degraded in the endoplasmic reticulum, similarly to human ATP7B-H1069Q. As a consequence, the mutant protein does not allow animals to counteract Cu toxicity. Notably, pharmacological correctors of ATP7B-H1069Q reduced Cu toxicity in cua-1 mutants indicating that similar pathogenic molecular pathways might be activated by the H/Q substitution and, therefore, targeted for rescue of ATP7B/CUA-1 function. Taken together, our findings suggest that the newly generated cua-1 mutant strain represents an excellent model for Cu toxicity studies in WD., (© 2023 The Authors. Traffic published by John Wiley & Sons Ltd.)

According to the amyloid hypothesis, in the early phases of Alzheimer's disease (AD), small soluble prefibrillar aggregates of the amyloid β-peptide (Aβ) interact with neuronal membranes, causing neural impairment. Such highly reactive and toxic species form spontaneously and transiently in the amyloid building pathway. A therapeutic strategy consists of the recruitment of these intermediates, thus preventing aberrant interaction with membrane components (lipids and receptors), which in turn may trigger a cascade of cellular disequilibria. Milk α s1 -Casein is an intrinsically disordered protein that is able to inhibit Aβ amyloid aggregation in vitro , by sequestering transient species. In order to test α s1 -Casein as an inhibitor for the treatment of AD, it needs to be delivered in the place of action. Here, we demonstrate the use of large unilamellar vesicles (LUVs) as suitable nanocarriers for α s1 -Casein. Proteo-LUVs were prepared and characterized by different biophysical techniques, such as multiangle light scattering, atomic force imaging, and small-angle X-ray scattering; α s1 -Casein loading was quantified by a fluorescence assay. We demonstrated on a C. elegans AD model the effectiveness of the proposed delivery strategy in vivo . Proteo-LUVs allow efficient administration of the protein, exerting a positive functional readout at very low doses while avoiding the intrinsic toxicity of α s1 -Casein. Proteo-LUVs of α s1 -Casein represent an effective proof of concept for the exploitation of partially disordered proteins as a therapeutic strategy in mild AD conditions.

In this case we briefly describe the case of an old woman presenting with acute exertional dyspnea due to hyperacute Sapien Valve thrombosis., (© 2023 Wiley Periodicals LLC.)

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy., Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website., Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and ≥40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity ( P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001)., Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO 2 -PDA have excellent colloidal stability in serum-supplemented culture media, even after long-term (24 h) exposure, showing no cytotoxic or genotoxic effects in vitro and ex vivo. Physiological responses, evaluated in vivo using Caenorhabditis elegans as the animal model, showed no impact on fertility and embryonic viability, induction of an oxidative stress response, and a mild impact on animal locomotion. These tests indicate that the synergistic combination of the silica matrix and PDA coating we developed effectively protects the SPIONs, providing enhanced colloidal stability and excellent biocompatibility.

Background: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand better how different echocardiographic modalities are used and accessed in Italy., Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved via an electronic survey based on a structured questionnaire, uploaded on the SIECVI website., Results: Data were obtained from 228 echocardiographic laboratories: 112 centers (49%) in the northern, 43 centers (19%) in the central, and 73 (32%) in the southern regions. During the month of observation, we collected 101,050 transthoracic echocardiography (TTE) examinations performed in all centers. As concern other modalities there were performed 5497 transesophageal echocardiography (TEE) examinations in 161/228 centers (71%); 4057 stress echocardiography (SE) examinations in 179/228 centers (79%); and examinations with ultrasound contrast agents (UCAs) in 151/228 centers (66%). We did not find significant regional variations between the different modalities. The usage of picture archiving and communication system (PACS) was significantly higher in the northern (84%) versus central (49%) and southern (45%) centers ( P < 0.001). Lung ultrasound (LUS) was performed in 154 centers (66%), without difference between cardiology and noncardiology centers. The evaluation of left ventricular (LV) ejection fraction was evaluated mainly using the qualitative method in 223 centers (94%), occasionally with the Simpson method in 193 centers (85%), and with selective use of the three-dimensional (3D) method in only 23 centers (10%). 3D TTE was present in 137 centers (70%), and 3D TEE in all centers where TEE was done (71%). The assessment of LV diastolic function was done routinely in 80% of the centers. Right ventricular function was evaluated using tricuspid annular plane systolic excursion in all centers, using tricuspid valve annular systolic velocity by tissue Doppler imaging in 53% of the centers, and using fractional area change in 33% of the centers. When we divided into cardiology (179, 78%) and noncardiology (49, 22%) centers, we found significant differences in the SE (93% vs. 26%, P < 0.001), TEE (85% vs. 18%), UCA (67% vs. 43%, P < 0001), and STE (87% vs. 20%, P < 0.001). The incidence of LUS evaluation was similar between the cardiology and noncardiology centers (69% vs. 61%, P = NS)., Conclusions: This nationwide survey demonstrated that digital infrastructures and advanced echocardiography modalities, such as 3D and STE, are widely available in Italy with a notable diffuse uptake of LUS in the core TTE examination, a suboptimal diffusion of PACS recording, and conservative use of UCA, 3D, and strain. There are significant differences between northern and central-southern regions and echocardiographic laboratories that pertain to the cardiac unit. This inhomogeneous distribution of technology represents one of the main issues that must be solved to standardize the practice of echocardiography., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)