A mechanism-based operational definition and classification of hypercholesterolemia

In contrast to strong evidence-based clinical recommendations for lipid-lowering treatment, there is no analogous definitive diagnostic definition of hypercholesterolemia and its various subtypes. For many clinicians, guideline indications for hypolipidemic treatment can become broadly conflated with hypercholesterolemia in a non-specific sense. In this statement, we propose a unified definition and mechanism-based classification of hypercholesterolemia, which in turn should help to stratify patients and guide efficient diagnosis without interfering with the current strategies of ASCVD risk reduction

J-PLUS: A wide-field multi-band study of the M15 globular cluster. Evidence of multiple stellar populations in the RGB

The Javalambre Photometric Local Universe Survey (J-PLUS) provides wide field-of-view images in 12 narrow, intermediate and broad-band filters optimized for stellar photometry. Here we have applied J-PLUS data for the first time for the study of Galactic GCs using science verification data obtained for the very metal-poor GC M\,15. Our J-PLUS data provide low-resolution spectral energy distributions covering the near-UV to the near-IR, allowing us to search for MPs based on pseudo-spectral fitting diagnostics. J-PLUS CMDs are found to be particularly useful to search for splits in the sequences formed by the upper red giant branch (RGB) and asymptotic giant branch (AGB) stars. We interpret these split sequences as evidence for the presence of MPs. This demonstrates that the J-PLUS survey will have sufficient spatial coverage and spectral resolution to perform a large statistical study of GCs through multi-band photometry in the coming years.Comment: 11 pages, 11 figures. Accepted for publication @ A&

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia

<p>Abstract</p> <p>Background</p> <p>Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.</p> <p>We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.</p> <p>Results</p> <p>A total of 29 gene sequence variants were reported in 117(76.0%) of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation), and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45). The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants.</p> <p>Conclusions</p> <p>Twenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.</p

J-PLUS: Detecting and studying extragalactic globular clusters. The case of NGC 1023.

Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Context. Extragalactic globular clusters (GCs) are key objects in studies of galactic histories. The advent of wide-field surveys, such as the Javalambre Photometric Local Universe Survey (J-PLUS), offers new possibilities for the study of these systems. Aims. We performed the first study of GCs in J-PLUS to recover information on the history of NGC 1023, taking advantage of wide-field images and 12 filters. Methods. We developed the semiautomatic pipeline GCFinder for detecting GC candidates in J-PLUS images, which can also be adapted to similar surveys. We studied the stellar population properties of a sub-sample of GC candidates using spectral energy distribution (SED) fitting. Results. We found 523 GC candidates in NGC 1023, about 300 of which are new. We identified subpopulations of GC candidates, where age and metallicity distributions have multiple peaks. By comparing our results with the simulations, we report a possible broad age-metallicity relation, supporting the notion that NGC 1023 has experienced accretion events in the past. With a dominating age peak at 1010 yr, we report a correlation between masses and ages that suggests that massive GC candidates are more likely to survive the turbulent history of the host galaxy. Modeling the light of NGC 1023, we find two spiral-like arms and detect a displacement of the galaxy’s photometric center with respect to the outer isophotes and center of GC distribution (~700pc and ~1600pc, respectively), which could be the result of ongoing interactions between NGC 1023 and NGC 1023A. Conclusions. By studying the GC system of NGC 1023 with J-PLUS, we showcase the power of multi-band surveys for these kinds of studies and we find evidence to support the complex accretion history of the host galaxy. © D. de Brito Silva et al. 2022.D.B.S. also acknowledges Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2017J00204-6 for the financial support provided for the development of this project. P.C. acknowledges support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under grant 310041/2018-0 and from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2018J05392-8. A.C.S. acknowledges funding from CNPq and the Rio Grande do Sul Research Foundation (FAPERGS) through grants CNPq-403580/2016-1, CNPq-11153/2018-6, PqG/FAPERGS-17/2551-0001, FAPERGS/CAPES 19/2551-0000696-9 and L’Oréal UNESCO ABC Para Mulheres na Ciência and the Chinese Academy of Sciences (CAS) President’s International Fellowship Initiative (PIFI) through grant E085201009. G.B. acknowledges financial support from the National Autonomous University of México (UNAM) through grant DGAPA/PAPIIT IG100319 and from CONACyT through grant CB2015-252364. J.V. acknowledges the technical members of the UPAD for their invaluable work: Juan Castillo, Tamara Civera, Javier Hernández, Ángel López, Alberto Moreno, and David Muniesa. J.A.H.J. acknowledges Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), process number 2021J08920-8. A.E. acknowledges the financial support from the Spanish Ministry of Science and Innovation and the European Union – NextGenerationEU through the Recovery and Resilience Facility project ICTS-MRR-2021-03-CEFCA and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under grant 313285/2020-9 D.A.F. thanks the ARC for financial assistance via DP170102344. Y.J.-T has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 898633. Y.J-T. also acknowledges financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). Based on observations made with the JAST80 telescope telescope/s at the Observatorio Astrofísico de Javalambre, in Teruel, owned, managed, and operated by the Centro de Estudios de Física del Cosmos de Aragón. We thank the Centro de Estudios de Física del Cosmos de Aragón for the allocation of the Director’s Discretionary Time to this program. We thank the OAJ Data Processing and Archiving Unit (UPAD) for reducing and calibrating the OAJ data used in this work. Funding for the J-PLUS Project has been provided by the Governments of Spain and Aragón through the Fondo de Inversiones de Teruel; the Aragón Government through the Research Groups E96, E103, and E16_17R; the Spanish Ministry of Science, Innovation, and Universities (MCIU/AEI/FEDER, UE) with grants PGC2018-097585-B-C21 and PGC2018-097585-B-C22; the Spanish Ministry of Economy and Competitiveness (MINECO) under AYA2015-66211-C2-1-P, AYA2015-66211-C2-2, AYA2012-30789, and ICTS-2009-14; and European FEDER funding (FCDD10-4E-867, FCDD13-4E-2685). The Brazilian agencies FINEP, FAPESP, and the National Observatory of Brazil have also contributed to this project. This work has made use of the computing facilities of the Laboratory of Astroinformatics (IAG/USP, NAT/Unicsul), whose purchase was made possible by the Brazilian agency FAPESP (grant 2009/54006-4) and the INCT-A.Peer reviewe

The Apache Point Observatory Galactic Evolution Experiment (APOGEE)

The Apache Point Observatory Galactic Evolution Experiment (APOGEE), one of the programs in the Sloan Digital Sky Survey III (SDSS-III), has now completed its systematic, homogeneous spectroscopic survey sampling all major populations of the Milky Way. After a three-year observing campaign on the Sloan 2.5 m Telescope, APOGEE has collected a half million high-resolution (R ~ 22,500), high signal-to-noise ratio (>100), infrared (1.51–1.70 μm) spectra for 146,000 stars, with time series information via repeat visits to most of these stars. This paper describes the motivations for the survey and its overall design—hardware, field placement, target selection, operations—and gives an overview of these aspects as well as the data reduction, analysis, and products. An index is also given to the complement of technical papers that describe various critical survey components in detail. Finally, we discuss the achieved survey performance and illustrate the variety of potential uses of the data products by way of a number of science demonstrations, which span from time series analysis of stellar spectral variations and radial velocity variations from stellar companions, to spatial maps of kinematics, metallicity, and abundance patterns across the Galaxy and as a function of age, to new views of the interstellar medium, the chemistry of star clusters, and the discovery of rare stellar species. As part of SDSS-III Data Release 12 and later releases, all of the APOGEE data products are publicly available

First international descriptive and interventional survey for cholesterol and non-cholesterol sterol determination by gas- and liquid- chromatography–Urgent need for harmonisation of analytical methods

Serum concentrations of lathosterol, the plant sterols campesterol and sitosterol and the cholesterol metabolite 5α-cholestanol are widely used as surrogate markers of cholesterol synthesis and absorption, respectively. Increasing numbers of laboratories utilize a broad spectrum of well-established and recently developed methods for the determination of cholesterol and non-cholesterol sterols (NCS). In order to evaluate the quality of these measurements and to identify possible sources of analytical errors our group initiated the first international survey for cholesterol and NCS. The cholesterol and NCS survey was structured as a two-part survey which took place in the years 2013 and 2014. The first survey part was designed as descriptive, providing information about the variation of reported results from different laboratories. A set of two lyophilized pooled sera (A and B) was sent to twenty laboratories specialized in chromatographic lipid analysis. The different sterols were quantified either by gas chromatography-flame ionization detection, gas chromatography- or liquid chromatography-mass selective detection. The participants were requested to determine cholesterol and NCS concentrations in the provided samples as part of their normal laboratory routine. The second part was designed as interventional survey. Twenty-two laboratories agreed to participate and received again two different lyophilized pooled sera (C and D). In contrast to the first international survey, each participant received standard stock solutions with defined concentrations of cholesterol and NCS. The participants were requested to use diluted calibration solutions from the provided standard stock solutions for quantification of cholesterol and NCS. In both surveys, each laboratory used its own internal standard (5α-cholestane, epicoprostanol or deuterium labelled sterols). Main outcome of the survey was, that unacceptably high interlaboratory variations for cholesterol and NCS concentrations are reported, even when the individual laboratories used the same calibration material. We discuss different sources of errors and recommend all laboratories analysing cholesterol and NCS to participate in regular quality control programs

Extracellular vesicles in atherosclerosis: Current and forthcoming impact?

Atherosclerosis is the main pathogenic substrate for cardiovascular diseases (CVDs). Initially categorized as a passive cholesterol storage disease, nowadays, it is considered an active process, identifying inflammation among the key players for its initiation and progression. Despite these advances, patients with CVDs are still at high risk of thrombotic events and death, urging to deepen into the molecular mechanisms underlying atherogenesis, and to identify novel diagnosis and prognosis biomarkers for their stratification. In this context, extracellular vesicles (EVs) have been postulated as an alternative in search of novel biomarkers in atherosclerotic diseases, as well as to investigate the crosstalk between the cells participating in the processes leading to arterial remodelling. EVs are nanosized lipidic particles released by most cell types in physiological and pathological conditions, that enclose lipids, proteins, and nucleic acids from parental cells reflecting their activation status. First considered cellular waste disposal systems, at present, EVs have been recognized as active effectors in a myriad of cellular processes, and as potential diagnosis and prognosis biomarkers also in CVDs. This review summarizes the role of EVs as potential biomarkers of CVDs, and their involvement into the processes leading to atherosclerosis. La aterosclerosis es el principal sustrato patogénico de las enfermedades cardiovasculares (ECV). Considerada inicialmente como un depósito pasivo de colesterol, hoy se asume que es un proceso activo, donde la inflamación juega un papel clave en su inicio y progresión. A pesar de los avances realizados, los pacientes con ECV presentan alto riesgo de episodios trombóticos y elevada mortalidad, por lo que sigue siendo necesario profundizar en los mecanismos de la aterogénesis e identificar nuevos biomarcadores diagnósticos y pronósticos para estratificar el riesgo. En este sentido, se ha postulado que las vesículas extracelulares (EV) podrían representar nuevos biomarcadores de la enfermedad aterosclerótica, siendo de interés investigar su participación en la comunicación intercelular que favorece el remodelado arterial. Las EV son partículas lipídicas liberadas por numerosas células en condiciones fisiológicas y patológicas, que contienen lípidos, proteínas y ácidos nucleicos procedentes de las células parentales. Consideradas inicialmente como material de desecho, hoy se sabe que son efectores activos de numerosos procesos celulares, constituyendo biomarcadores potenciales con significado diagnóstico y pronóstico en la ECV. En esta revisión se sintetiza el papel de las EV como biomarcadores potenciales de las ECV y su participación en procesos que favorecen la aterosclerosis

Impact of conducting a genetic study on the management of familial hypercholesterolemia

[Background] Clinically diagnosed familial hypercholesterolemia (FH) may require a genetic test (GT) to confirm diagnosis. GT availability/accessibility is resource-dependent and usually restricted to specialized clinics. While GT has a diagnostic value, it has not yet defined its impact on long-term management and prognosis of FH.[Objective] The aim was to identify the clinical characteristics associated with the request for a GT in suspected heterozygous FH.[Methods] Retrospective study including adult patients with clinically suspected to be FH. Positive GT (GT+) was defined as having a pathogenic/likely pathogenic variant. Patients were stratified based on whether they had a genetic study conducted, and among those with a genetic study, according to those who did or did not have a GT+.[Results] From 4854 patients included, 3090 were performed a GT (GT+: 2113). Median follow-up: 6.2 years. A younger age, FH-related physical signs, premature coronary disease, higher low-density lipoprotein cholesterol (LDLc) and lower body mass index and triglycerides, associated higher odds of being conducted a genetic study. These patients had higher baseline LDLc (252 mg/dL vs. 211 mg/dL among clinically diagnosed patients) and experienced larger reductions over the follow-up (157.7 mg/dL vs. 113.5 mg/dL, respectively). A similar pattern was observed among patients with GT+ (vs. negative GT). LDLc target attainment was low but increased to 66–95% when a triple combination with statin/ezetimibe/proprotein convertase subtilisin kexin type 9-inhibitor was used. Cardiovascular events occurred in 3.2% and 3.1% of patients who conducted/not conducted a genetic study. Patients conducted a genetic analysis and those with GT+ tended to present the events earlier.[Conclusions] Genetic study, vs. having a clinical-only diagnosis, impacts the management of FH. Cardiovascular prognosis was similar in both groups, perhaps as a result of the more intensive management of patients with a genetic study.We want to particularly acknowledge the patients and the Biobank of the Aragon Health System (PT17/0015/0039) integrated in the Spanish National Biobanks Network for their collaboration. AJV-V acknowledges support from the Program “Beatriz Galindo” from the Ministry of Universities, Spain, and University of Seville, Spain.Peer reviewe