Detecting familial hypercholesterolemia: An observational study leveraging mandatory universal pediatric total cholesterol screening in Slovakia.

Background: In Slovakia, a mandatory national universal pediatric total cholesterol (TC) screening program is in place to identify cases of familial hypercholesterolemia (FH). However, the program's effectiveness has not been systematically assessed.

Objective: This study aimed to estimate the prevalence of FH among parents of children that had elevated TC levels identified during screening.

LDLR gene rearrangements in Czech FH patients likely arise from one mutational event.

Background: Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements.

Methods: The breakpoint sequence was determined by PCR amplification and Sanger sequencing.

Coral larval settlement induction using tissue-associated and exuded coralline algae metabolites and the identification of putative chemical cues.

Reef-building crustose coralline algae (CCA) are known to facilitate the settlement and metamorphosis of scleractinian coral larvae. In recent decades, CCA coverage has fallen globally and degrading environmental conditions continue to reduce coral survivorship, spurring new restoration interventions to rebuild coral reef health. In this study, naturally produced chemical compounds (metabolites) were collected from two pantropical CCA genera to isolate and classify those that induce coral settlement.

The pathophysiology of cancer-mediated cardiac cachexia and novel treatment strategies: A narrative review.

Significance: Two of the leading causes of death worldwide are cancer and cardiovascular diseases. Most cancer patients suffer from a metabolic wasting syndrome known as cancer-induced cardiac cachexia, resulting in death in up to 30% of cancer patients. Main symptoms of this disease are severe cardiac muscle wasting, cardiac remodeling, and cardiac dysfunction.

Comparative Characterization of Immune Response in Sheep with Caseous Lymphadenitis through Analysis of the Whole Blood Transcriptome.

Caseous lymphadenitis (CL) is a chronic contagious disease that affects small ruminants and is characterized by the formation of pyogranulomas in lymph nodes and other organs. However, the pathogenesis of this disease and the response of the host genome to infection are not yet fully understood. This study aimed to investigate the whole blood transcriptome and evaluate differential gene expression during the later stages of CL in naturally infected ewes.

Notch Signaling in Acute Inflammation and Sepsis.

Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this pathway is also directly involved in the transmission of immune signals. Notch signaling per se does not have a clear pro- or anti-inflammatory effect, but rather its impact is highly dependent on the immune cell type and the cellular environment, modulating several inflammatory conditions including sepsis, and therefore significantly impacts the course of disease.

Possible effects of the MC4R Asp298Asn polymorphism on pig production traits under ad libitum versus restricted feeding.

The missense mutation Asp298Asn in the melanocortin 4 receptor (MC4R) is associated with daily gain or fatness in pigs (Sus scrofa domesticus). However, to the best of our knowledge, no study has directly compared the effects of the polymorphism between different feeding levels, even though diet plays a vital role in the swine industry. To explore possible differences, data from 439 mostly commercial hybrids fattened ad libitum and 119 commercial hybrids fattened with restricted feed ration were collected.

Genome-Wide Association Study for Body Conformation Traits and Fitness in Czech Holsteins.

The aim of this study was a genome-wide association study (GWAS) on conformation traits using 25,486 genotyped Czech Holsteins, with 35,227 common SNPs for each genotype. Linear trait records were collected between 1995 and 2020. The Interbull information from Multiple Across Country Evaluation (MACE) was included for bulls that mostly had daughter records in a foreign country.

Cardioprotective effects of preconditioning exercise in the female tumor bearing mouse.

Cancer cachexia, a metabolic wasting syndrome, affects up to 80% of cancer patients and leads to the death in up to 20% of cancer patients. While research is growing in the field, there are still no clear diagnostic criteria and cancer cachexia remains an untreated condition. Aerobic exercise has been shown to positively impact cachexia by slowing its development and attenuating muscle loss.

Genealogical analysis of European bison population revealed a growing up population despite very low genetic diversity.

In 1919, the European bison population became extinct in the wild. The rescue of the lowland subspecies and the whole species was achieved mainly thanks to individuals from the Białowieża Forest (Polish-Belarusian border). There are currently two breeding lines-the lowland (purebred B.

Increased prevalence of clonal hematopoiesis of indeterminate potential in hospitalized patients with COVID-19.

Clonal hematopoiesis of indeterminate potential (CHIP) leads to higher mortality, carries a cardiovascular risk and alters inflammation. All three aspects harbor overlaps with the clinical manifestation of COVID-19. This study aimed to identify the impact of CHIP on COVID-19 pathophysiology.

Millimeter-scale topography facilitates coral larval settlement in wave-driven oscillatory flow.

Larval settlement in wave-dominated, nearshore environments is the most critical life stage for a vast array of marine invertebrates, yet it is poorly understood and virtually impossible to observe in situ. Using a custom-built flume tank that mimics the oscillatory fluid flow over a shallow coral reef, we isolated the effect of millimeter-scale benthic topography and showed that it increases the settlement of slow-swimming coral larvae by an order of magnitude relative to flat substrates. Particle tracking velocimetry of flow fields revealed that millimeter-scale ridges introduced regions of flow recirculation that redirected larvae toward the substrate surface and decreased the local fluid speed, effectively increasing the window of time for larvae to settle.

The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification.

Purpose: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified.

Extracellular Lactate Acts as a Metabolic Checkpoint and Shapes Monocyte Function Time Dependently.

Elevated blood lactate levels are frequently found in critically ill patients and thought to result from tissue hypoperfusion and cellular oxygen shortage. Considering the close relationship between immune cell function and intracellular metabolism, lactate is more than a glycolytic waste molecule but able to regulate the immune response. Our aim was to elucidate the temporal and mechanistic effect of extracellular lactate on monocytes.

Rising temperature modulates pH niches of fen species.

Rising temperatures may endanger fragile ecosystems because their character and key species show different habitat affinities under different climates. This assumption has only been tested in limited geographical scales. In fens, one of the most endangered ecosystems in Europe, broader pH niches have been reported from cold areas and are expected for colder past periods.

Assisted gene flow using cryopreserved sperm in critically endangered coral.

Assisted gene flow (AGF) is a conservation intervention to accelerate species adaptation to climate change by importing genetic diversity into at-risk populations. Corals exemplify both the need for AGF and its technical challenges; corals have declined in abundance, suffered pervasive reproductive failures, and struggled to adapt to climate change, yet mature corals cannot be easily moved for breeding, and coral gametes lose viability within hours. Here, we report the successful demonstration of AGF in corals using cryopreserved sperm that was frozen for 2 to 10 y.

A case of homozygous familial hypercholesterolemia with an atypical phenotype and delayed clinical symptoms.

We describe the casuistry of a homozygous familial hypercholesterolemia female patient with a biallelic missense variant (NM_000527.4:c.1775G>A, p.

The density, nanohardness and some optical properties of As-S and As-Se chalcogenide bulk glasses and thin films.

Amorphous AsS, AsSe and AsSe bulk glasses and thin films were prepared by the melt quenching technique and vacuum thermal evaporation, respectively, on different substrates. The density () - determined by the simple and cheap method of precise weighting, refractive index (), structural arrangement - inferred from Raman spectroscopy, and nanohardness ( ) were determined for all the studied materials in both bulk and thin film states. It is found that regardless of the chemical composition, the bulk glass density, refractive index and nanohardness are higher in comparison with those of the corresponding virgin and by annealing relaxed thin films, and the observed differences are discussed.

Genetics of Familial Hypercholesterolemia: New Insights.

Familial hypercholesterolemia (FH) is one of the most common monogenic diseases, leading to an increased risk of premature atherosclerosis and its cardiovascular complications due to its effect on plasma cholesterol levels. Variants of three genes (, and ) are the major causes of FH, but in some probands, the FH phenotype is associated with variants of other genes. Alternatively, the typical clinical picture of FH can result from the accumulation of common cholesterol-increasing alleles (polygenic FH).

Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact.

Pathogenic variants in the low density lipoprotein receptor gene are associated with familial hypercholesterolemia. Some of these variants can result in incorrect folding of the LDLR protein, which is then accumulated inside the cell and cannot fulfill its function to internalize LDL particles. We analyzed the functional impact of 10 LDLR variants localized in the beta-propeller of epidermal growth factor precursor homology domain.

A case of autosomal recessive hypercholesterolemia caused by a new variant in the LDL receptor adaptor protein 1 gene.

We report a new variant in the LDLRAP1 gene associated with autosomal recessive hypercholesterolemia in a woman of central European ancestry.