Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance of hyperalphalipoproteinemia. Epidemiological studies have suggested that HDL-C is inversely correlated with cardiovascular (CV) risk, but recent Mendelian randomization data have shown a lack of atheroprotective causal effects of HDL-C. This review will focus on primary forms of HALP, the role of polygenic inheritance on HDL-C, associated risk for cardiovascular diseases and possible treatment options

Metabolomic patterns associated to QTc interval in shiftworkers: an explorative analysis

Objectives: 1H NMR-metabolomic approach was used to investigate QTc interval correlation with plasma metabolic profiles in shiftworkers. Methods: Socio-demographic data, electrocardiographic QTc interval and plasma metabolic profiles from 32 male shiftworkers, were correlated by multivariate regression analysis. Results: We found a positive correlation between QTc interval values, body mass index, glycemia and lactate level and a negative correlation between QTc interval and both pyroglutamate and 3-hydroxybutyrate plasma level. Conclusions: Our analysis provides evidence of the association between clinical, metabolic profiles and QTc interval values. This could be used to identify markers of early effects and/or susceptibility in shiftworker

The vaccinaTion & Hpv Knowledge (THinK) questionnaire: a reliability and validity study on a sample of women living in Sicily (southern-Italy)

Objective The aim of this study was to introduce the VaccinaTion & Hpv Knowledge (THinK) questionnaire to assess knowledge about human papillomavirus (HPV) and attitude to HPV-vaccination. Its reliability and validity was demonstrated in a sample of women living in Sicily (southern Italy). Methods A cross-sectional survey was conducted on a sample of 220 women at the “Paolo Giaccone” University Hospital in Palermo (Sicily), aged 18–61. Data were analyzed through Cronbach’s alpha and exploratory factor analysis, followed by a structural equation model with measurement component. The two-level data structure was explicitly considered. Results Three dimensions were found: “knowledge of HPV infection (kHPV), “Attitude to be vaccinated against HPV (aHPV)” and “Knowledge about vaccines (KV)” (97% overall explained variance). Internal consistency was good for the whole questionnaire (0.82) and the first dimension (0.88) and acceptable for the second (0.78) and the third dimension (0.73). 23% of women showed no or little knowledge of HPV and 44.3% of women had no or little knowledge about HPV induced lesions. Discussion The use of a validated questionnaire may serve as a useful measure to assess general knowledge about HPV and attitude towards vaccination against HPV in the primary prevention setting

Characterisation of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicronaemia syndrome (MCS): establishment of an FCS clinical diagnostic score

Data presented in this article are supplementary material to our article entitled "Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recom mendations and proposal of an "FCS Score" (Moulin et al., 2018, in press). The data describe the genotypes of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicro naemia syndrome (MCS), from the validation and replication cohorts

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Borexino's search for low-energy neutrinos associated with gravitational wave events from GWTC-3 database

The search for neutrino events in correlation with gravitational wave (GW) events for three observing runs (O1, O2 and O3) from 09/2015 to 03/2020 has been performed using the Borexino data-set of the same period. We have searched for signals of neutrino-electron scattering with visible energies above 250 keV within a time window of 1000 s centered at the detection moment of a particular GW event. The search was done with three visible energy thresholds of 0.25, 0.8 and 3.0 MeV.Two types of incoming neutrino spectra were considered: the mono-energetic line and the spectrum expected from supernovae. The same spectra were considered for electron antineutrinos detected through inverse beta-decay (IBD) reaction. GW candidates originated by merging binaries of black holes (BHBH), neutron stars (NSNS) and neutron star and black hole (NSBH) were analysed separately. Additionally, the subset of most intensive BHBH mergers at closer distances and with larger radiative mass than the rest was considered. In total, follow-ups of 74 out of 93 gravitational waves reported in the GWTC-3 catalog were analyzed and no statistically significant excess over the background was observed. As a result, the strongest upper limits on GW-associated neutrino and antineutrino fluences for all flavors (\nu_e, \nu_\mu, \nu_\tau) have been obtained in the (0.5 - 5.0) MeV neutrino energy range.Comment: 13 pages, 8 figure

Novel techniques for alpha/beta pulse shape discrimination in Borexino

Borexino could efficiently distinguish between alpha and beta radiation in its liquid scintillator by the characteristic time profile of their scintillation pulse. This alpha/beta discrimination, first demonstrated at the tonne scale in the Counting Test Facility prototype, was used throughout the lifetime of the experiment between 2007 and 2021. With this method, alpha events are identified and subtracted from the beta-like solar neutrino events. This is particularly important in liquid scintillator as alpha scintillation is quenched many-fold. In Borexino, the prominent Po-210 decay peak was a background in the energy range of electrons scattered from Be-7 solar neutrinos. Optimal alpha-beta discrimination was achieved with a "multi-layer perceptron neural network", which its higher ability to leverage the timing information of the scintillation photons detected by the photomultiplier tubes. An event-by-event, high efficiency, stable, and uniform pulse shape discrimination was essential in characterising the spatial distribution of background in the detector. This benefited most Borexino measurements, including solar neutrinos in the \pp chain and the first direct observation of the CNO cycle in the Sun. This paper presents the key milestones in alpha/beta discrimination in Borexino as a term of comparison for current and future large liquid scintillator detectorsComment: 13 pages, 14 figure

Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting. Methods and results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016). Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH

Experimental Detection of the CNO Cycle

Borexino recently reported the first experimental evidence for a CNO neutrino. Since this process accounts for only about 1% of the Sun’s total energy production, the associated neutrino flux is remarkably low compared to that of the pp chain, the dominant hydrogen-burning process. This experimental evidence for the existence of CNO neutrinos was obtained using a highly radio-pure Borexino liquid scintillator. Improvements in the thermal stabilization of the detector over the last five years have allowed us to exploit a method of constraining the rate of 210Bi background. Since the CNO cycle is dominant in massive stars, this result is the first experimental evidence of a major stellar hydrogen-to-helium conversion mechanism in the Universe

Solar and geoneutrinos

Thanks to the progress of neutrino physics, today we are able of exploiting neutrinos as a tool to study astrophysical objects. The latter in turn serve as unique sources of elusive neutrinos, which fundamental properties are still to be understood. This contribution attempts to summarize the latest results obtained by measuring neutrinos emitted from the Sun and geoneutrinos produced in radioactive decays inside the Earth, with a particular focus on a recent discovery of the CNO-cycle solar neutrinos by Borexino. Comprehensive measurement of the pp-chain solar neutrinos and the first directional detection of sub-MeV solar neutrinos by Borexino, the updated 8B solar neutrino results of Super-Kamiokande, as well as the latest Borexino and KamLAND geoneutrino measurements are also discussed