Age and Sex Differences in Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis.

Background: Ageing is a significant risk factor for carotid atherosclerosis, affecting over a billion people worldwide. Carotid intima-media thickness (cIMT) is a surrogate marker for cardiovascular disease (CVD) risk, with age- and sex-related differences in levels and progression. The onset of clinical manifestations of CVD in women is delayed by about 10 years compared to men.

Determinants of Carotid Wall Echolucency in a Cohort of European High Cardiovascular Risk Subjects: A Cross-Sectional Analysis of IMPROVE Baseline Data.

Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima-media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM.

Role of antibody engineering in generation of derivatives starting from MOv19 MAb: 40 years of biological/therapeutic tools against folate receptor alfa.

In the 1980s, we developed and characterized numerous murine monoclonal antibodies (MAbs) directed against human tumor-associated antigens. This mini review is focused on the generation of derivatives of an anti-folate receptor α (FRα) MAbs, named MOv19, exploiting the antibody-engineering progresses in the last 40 years. The FRα location on the luminal surface of proliferating epithelial cells, inaccessible to circulation, versus its over-expression in the entire surface of numerous carcinomas suggested a role for anti-FRα MAbs in the diagnosis and/or treatment of solid tumors.

Validity of Anti-PSMA ScFvD2B as a Theranostic Tool: A Narrative-Focused Review.

Prostate cancer (PCa) is the second leading cause of cancer among men, and its diagnosis and adequate staging are fundamental. Among the biomarkers identified in recent years for PCa management, prostate-specific-membrane-antigen (PSMA), physiologically expressed at a low level on healthy prostate and in other normal tissues and highly overexpressed in PCa, represents a reliable marker ideal for imaging and therapy. The development of anti-PSMA antibodies, such as D2B, demonstrated slow clearance of intact antibodies compared with fragments resulting in low tumor-to-blood ratios; however, the modular structural and functional nature of antibodies allowed the generation of smaller fragments, such as scFvs.

Assessment of New Coronary Features on Quantitative Coronary Angiographic Images With Innovative Unsupervised Artificial Adaptive Systems: A Proof-of-Concept Study.

The Active Connection Matrixes (ACMs) are unsupervised artificial adaptive systems able to extract from digital images features of interest (edges, tissue differentiation, etc.) unnoticeable with conventional systems. In this proof-of-concept study, we assessed the potentiality of ACMs to increase measurement precision of morphological structures (e.

Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis-The IMPROVE Study.

(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis.

The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study.

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk.

Selinexor Sensitizes TRAIL-R2-Positive TNBC Cells to the Activity of TRAIL-R2xCD3 Bispecific Antibody.

Triple-negative breast cancer (TNBC) is an aggressive disease with poor prognosis and limited therapeutic options. Recent advances in the immunotherapy field have enabled the development of new treatment strategies, among which the use of bispecific antibodies (BsAbs), able to redirect T cells against tumors, has shown promising results. In particular, a BsAb that uses TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) as a target was constructed and demonstrated good results in redirecting CD3 T cells to kill TRAIL-R2-expressing TNBC cells.

Relationship between Influenza Vaccination Coverage Rate and COVID-19 Outbreak: An Italian Ecological Study.

The lack of specific vaccines or drugs against coronavirus disease 2019 (COVID-19) warrants studies focusing on alternative clinical approaches to reduce the spread of this pandemic disease. In this study, we investigated whether anti-influenza vaccination plays a role in minimizing the diffusion of COVID-19 in the Italian population aged 65 and over. Four COVID-19 outcomes were used: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, hospitalizations for COVID-19 symptoms, admissions to intensive care units for reasons related to SARS-CoV-2, and deaths attributable to COVID-19.

Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study.

Background And Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n = 3673) of men (47.

Traditional Risk Factors are Causally Related to Carotid Intima-Media Thickness Progression: Inferences from Observational Cohort Studies and Interventional Trials.

In the present review, associations between traditional vascular risk factors (VRFs) and carotid intimamedial thickness progression (C-IMTp) as well as the effects of therapies for VRFs control on C-IMTp were appraised to infer causality between each VRF and C-IMTp. Cohort studies indicate that smoking, binge drinking, fatness, diabetes, hypertension and hypercholesterolemia are associated with accelerated C-IMTp. An exception is physical activity, with mixed data.

A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy.

T-cell-based immunotherapy strategies have profoundly improved the clinical management of several solid tumors and hematological malignancies. A recently developed and promising immunotherapy approach is to redirect polyclonal MHC-unrestricted T lymphocytes toward cancer cells by bispecific antibodies (bsAbs) that engage the CD3 complex and a tumor-associated antigen (TAA). The TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) is an attractive immunotherapy target, frequently expressed by neoplastic cells, that we decided to exploit as a TAA.

Acceptance of a New Food Enriched in β-Glucans among Adolescents: Effects of Food Technology Neophobia and Healthy Food Habits.

The aim of the present study was to evaluate adolescents' acceptability of a novel flat bread modified by substituting a part of the wheat flour content with a powder rich in β-glucans, which can potentially provide health benefits. The effects of food technology neophobia and adolescents' food habits on hedonic perception of the developed product was also investigated. Two hundred and two adolescents (age range: 13-18 years; girls: 49.

Data on the association between a simplified Mediterranean diet score and the incidence of combined, cardio and cerebro vascular events.

Data presented in this article are related to the research article entitled "" [Veglia et al., 2018]. Data contain information about the incidence of cardiovascular events in a high-risk European population (IMPROVE study) [Baldassarre et al.

Anti-PSMA I-scFvD2B as a new immuno-PET tool for prostate cancer: preclinical proof of principle.

Background: Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET.

Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases.

Folate receptors and transporters and one-carbon metabolism continue to be important areas of study given their essential roles in an assortment of diseases and as targets for treatment of cancer and inflammation. Reflecting this, every 2 years, the Folate Receptor Society organizes an international meeting, alternating between North America and Europe, where basic and translational scientists, clinical oncologists and rheumatologists from both academia and industry convene in an informal setting. The 7th International Symposium on Folate Receptors and Transporters was held in Sant'Alessio Siculo (ME), Taormina, Italy from 1st to 5th of October 2018, organized by Dr.

A priori-defined Mediterranean-like dietary pattern predicts cardiovascular events better in north Europe than in Mediterranean countries.

Background: The Mediterranean Diet (MD) is a model of healthy eating contributing to a favorable health status, but its clinical usefulness is still debated. The aim of this study was to relate the adherence to MD with the incidence of cardio/cerebro-vascular events (VEs) in north and south European participants of the IMPROVE study.

Methods: IMPROVE is an observational, longitudinal, prospective cohort study involving 3703 individuals from five European countries (Finland, Sweden, Netherlands, France and Italy).

Novel pharmacological targets for calcific aortic valve disease: Prevention and treatments.

Calcific aortic valve disease (CAVD) is the most common valvular disorder in the elderly, with the incidence of 3% in general population of Western countries. The initial phase of CAVD is characterized by leaflet thickening and possible spotty calcification (i.e.

Design, selection and optimization of an anti-TRAIL-R2/anti-CD3 bispecific antibody able to educate T cells to recognize and destroy cancer cells.

Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or TRAIL-receptor agonistic monoclonal antibodies promote apoptosis in most cancer cells, and the differential expression of TRAIL-R2 between tumor and normal tissues allows its exploitation as a tumor-associated antigen. The use of these antibodies as anticancer agents has been extensively studied, but the results of clinical trials were disappointing. The observed lack of anticancer activity could be attributed to intrinsic or acquired resistance of tumor cells to this type of treatment.

Association of lifelong occupation and educational level with subclinical atherosclerosis in different European regions. Results from the IMPROVE study.

Background And Aims: We aimed to examine the association between socioeconomic status (SES) and subclinical atherosclerosis, as assessed by carotid intima-media-thickness (C-IMT) and to investigate whether the effect of social inequality on C-IMT is mediated by cardiovascular (CV) risk factors and whether it is dissimilar in men and women, and in different European countries.

Methods: We assessed the association of lifelong occupation and educational level with C-IMT in the IMPROVE study cohort including 3703 subjects (median age 64.4 years; 48% men) from Southern (Italy), Western (France and the Netherlands) and Northern Europe (Finland and Sweden).

Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification.

Background And Aims: Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMT) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMT in cardiovascular risk prediction and risk stratification.

Methods: The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMT.

Old and new oral anticoagulants: Food, herbal medicines and drug interactions.

The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.

Full preclinical validation of the 123I-labeled anti-PSMA antibody fragment ScFvD2B for prostate cancer imaging.

Purpose: In the context of prostate cancer (PCa) imaging, the aim of this study was to optimize (in vitro) the specificity and assess preclinically (in vivo) the tumor targeting properties of the 123I-scFvD2B antibody specific for prostate-specific membrane antigen (PSMA).

Experimental Design: The 123I-labeling conditions of the antibody fragment scFvD2B, produced in an eukaryotic system under GMP-compliant conditions, were optimized and assessed for purity and immunoreactivity. The specificity and potency of tumor uptake were tested in three preclinical in vivo models of subcutaneously xenografted human tumors expressing different levels of PSMA (LNCaP, naturally expressing PSMA; PC3-PIP and LS174T-PSMA, transfected with PSMA) or PC3 and LS174T, as negative controls, to assess the clearance, biodistribution and imaging potential of 123I-scFvD2B.

Effect of radiochemical modification on biodistribution of scFvD2B antibody fragment recognising prostate specific membrane antigen.

Antibody-based reagents represent a promising strategy as clinical diagnostic tools. Prostate cancer (PCa) is the second-leading cause of death in males in the Western population. There is a presently unmet need for accurate diagnostic tool to localize and define the extent of both primary PCa and occult recurrent disease.

Assessment and relevance of carotid intima-media thickness (C-IMT) in primary and secondary cardiovascular prevention.

Interventions aimed to prevent cardiovascular diseases (CVD) are more effective if administered to subjects carefully selected according to their CVD risk. Usually, this risk is evaluated on the basis of the presence and severity of conventional vascular risk factors (VRFs); however, atherosclerosis, the main pathologic substrate of CVD, is not directly revealed by VRFs. The measurement of the arterial wall, using imaging techniques, has increased the early identification of individuals prone to develop atherosclerosis and to quantify its changes over time.