Carotid intima-medial thickness in patients with severe hypertriglyceridemia.

Background And Aims: Severe hypertriglyceridemia (HTG), defined as plasma triglyceride (TG) concentration > 10 mmol/L, is relatively uncommon, and its implications for atherosclerotic cardiovascular disease (ASCVD) risk remain somewhat unclear. We evaluated the association between severe HTG and carotid intima-media thickness (IMT), a marker for ASCVD.

Methods: We studied three clinical cohorts: 88 patients with severe HTG (mean TG level 20.

Activation of MAP Kinase Pathway by Polyisoprenylated Cysteinyl Amide Inhibitors Causes Apoptosis and Disrupts Breast Cancer Cell Invasion.

Prognoses for TNBC remain poor due to its aggressive nature and the lack of therapies that target its "drivers". RASA1, a RAS-GAP or GTPase-activating protein whose activity inhibits RAS signaling, is downregulated in up to 77% of TNBC cases. As such, RAS proteins become hyperactive and similar in effect to mutant hyperactive RAS proteins with impaired GTPase activities.

Polyisoprenylated cysteinyl amide inhibitors deplete singly polyisoprenylated monomeric G-proteins in lung and breast cancer cell lines.

Finding effective therapies against cancers driven by mutant and/or overexpressed hyperactive G-proteins remains an area of active research. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) are agents that mimic the essential posttranslational modifications of G-proteins. It is hypothesized that PCAIs work as anticancer agents by disrupting polyisoprenylation-dependent functional interactions of the G-Proteins.

Clinical and genetic associations of deep learning-derived cardiac magnetic resonance-based left ventricular mass.

Left ventricular mass is a risk marker for cardiovascular events, and may indicate an underlying cardiomyopathy. Cardiac magnetic resonance is the gold-standard for left ventricular mass estimation, but is challenging to obtain at scale. Here, we use deep learning to enable genome-wide association study of cardiac magnetic resonance-derived left ventricular mass indexed to body surface area within 43,230 UK Biobank participants.

Donor and recipient human leukocyte antigen-G polymorphisms modulate the risk of adverse immunologic events following lung transplantation.

The long-term benefits of lung transplantation (LTx) are limited by pathogenic alloimmune responses that drive injury, inflammation, and chronic dysfunction. Human leukocyte antigen-G (HLA-G) plays a key role in the modulation of these pathways. This study assesses the impact of the HLA-G genotype on immunologic risk and survival following LTx.

LMNA Variants and Risk of Adult-Onset Cardiac Disease.

Background: Genetic variants in LMNA may cause cardiac disease, but population-level contributions of variants to cardiac disease burden are not well-characterized.

Objectives: We sought to determine the frequency and contribution of rare LMNA variants to cardiomyopathy and arrhythmia risk among ambulatory adults.

Methods: We included 185,990 UK Biobank participants with whole-exome sequencing.

Is Deprescription of Ezetimibe Safe in Familial Hypercholesterolemia Patients Taking Evolocumab?

We evaluated whether low-density lipoprotein cholesterol (LDL-C) levels in familial hypercholesterolemia patients on triple lipid-lowering therapy would remain below intensification threshold values after withdrawal of ezetimibe. We included 13 heterozygous familial hypercholesterolemia patients with vascular disease who were treated with statin + ezetimibe + evolocumab; ezetimibe was discontinued at the patients' request. After 3 months, LDL-C levels increased from 0.

Membrane vesicles from antibiotic-resistant Staphylococcus aureus transfer antibiotic-resistance to antibiotic-susceptible Escherichia coli.

Aim: Bacteria naturally produce membrane vesicles (MVs), which have been shown to contribute to the spread of multi-drug resistant bacteria (MDR) by delivering antibiotic-resistant substances to antibiotic-susceptible bacteria. Here, we aim to show that MVs from Gram-positive bacteria are capable of transferring β-lactam antibiotic-resistant substances to antibiotic-sensitive Gram-negative bacteria.

Materials And Methods: MVs were collected from a methicillin-resistant strain of Staphylococcus aureus (MRSA) and vesicle-mediated fusion with antimicrobial-sensitive Escherichia coli (RC85).

Lamin A/C missense variants: from discovery to functional validation.

Rare variants in the gene encoding nuclear lamin A/C are causal for more than a dozen diverse mendelian disorders. Defining the functional consequences of variants has been challenging given the pleiotropy of gene functions and potential pathogenic mechanisms. It is essential to develop trustworthy, scalable and rapidly deployable in vitro assays of function to enable timely assessment of missense variants that are being uncovered by high throughout next-generation sequencing.

Prevalence of severe hypertriglyceridemia and pancreatitis in familial partial lipodystrophy type 2.

Familial partial lipodystrophy (FPLD) is a rare Mendelian condition listed in the differential diagnosis of severe hypertriglyceridemia (HTG) and pancreatitis. Here we determined the prevalence of severe HTG and pancreatitis among a cohort of 74 FPLD patients assessed in a lipid clinic. We studied lipid profiles from individuals with either of the two most common pathogenic monoallelic variants in LMNA, namely p.

Volanesorsen for treatment of familial chylomicronemia syndrome.

Introduction: Familial chylomicronemia syndrome (FCS) is a rare subtype of severe hypertriglyceridemia that affects ~1 in 100, 000 to 1,000,000 individuals. The major risk to health is acute pancreatitis. FCS is defined by biallelic loss-of-function mutations in one of five canonical genes that encode proteins critical to lipolysis of large triglyceride-rich lipoprotein particles.

Evaluating Polygenic Risk Scores in "Lone" Atrial Fibrillation.

Background: Polygenic scores incorporating varying numbers of single nucleotide polymorphisms (SNPs) have been demonstrated to exert a prominent role in atrial fibrillation (AF). We sought to compare the relative discriminatory capacities of 2 previously validated polygenic scores in "lone" AF.

Methods: A total of 186 lone AF cases of European ancestry underwent SNP genotyping.

Poly (I:C)-Potentiated Vaccination Enhances T Cell Response in Olive Flounder () Providing Protection against Viral Hemorrhagic Septicemia Virus (VHSV).

Viral hemorrhagic septicemia (VHS), caused by viral hemorrhagic septicemia virus (VHSV), is a viral disease affecting teleosts, and is the major cause of virus-related deaths in olive flounder (). Research has focused on ways to control VHS, and recently, the use of polyinosinic-polycytidylic acid poly (I:C)-potentiated vaccination has been investigated, whereby fish are injected with poly (I:C) and then with live pathogenic virus, resulting in a significant decrease in VHSV-related mortality. T cell responses were investigated in the present study after vaccinating olive flounder with poly (I:C)-potentiated vaccination to understand the ability of poly (I:C) to induce T cell immunity.

Lipid effects of sodium-glucose cotransporter 2 inhibitors.

Purpose Of Review: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used antihyperglycemic drugs that show remarkable cardiorenal protective effects in patients with or without type 2 diabetes. Furthermore, they are effective among patients across a wide range of baseline renal and cardiac function. Numerous mechanisms have been evaluated to understand these remarkable clinical benefits.

Enrichment of loss-of-function and copy number variants in ventricular cardiomyopathy genes in 'lone' atrial fibrillation.

Aims: Atrial fibrillation (AF) is a complex heritable disease whose genetic underpinnings remain largely unexplained, though recent work has suggested that the arrhythmia may develop secondary to an underlying atrial cardiomyopathy. We sought to evaluate for enrichment of loss-of-function (LOF) and copy number variants (CNVs) in genes implicated in ventricular cardiomyopathy in 'lone' AF.

Methods And Results: Whole-exome sequencing was performed in 255 early onset 'lone' AF cases, defined as arrhythmia onset prior to 60 years of age in the absence of known clinical risk factors.

Liver Injury Associated With Ezetimibe Monotherapy.

Statin intolerance, primarily myalgia, is not uncommon in patients treated for elevated low-density lipoprotein cholesterol. Nonstatin drugs, such as ezetimibe, can spare patients from statin exposure, while still reducing low-density lipoprotein cholesterol. Ezetimibe is generally very well tolerated, although gastrointestinal and musculoskeletal symptoms have been occasionally reported.

Molecular characterization of a Bacillus thuringiensis strain from Argentina, toxic against Lepidoptera and Coleoptera, based on its whole-genome and Cry protein analysis.

The insecticidal proteins of Bacillus thuringiensis are used in formulations of spore-crystal complexes and their genes have been incorporated into several crops, providing a model for genetic engineering in agriculture. Despite the variability of the Cry proteins described so far, it is still necessary to look for toxins with a broad spectrum of action, since a significant number of pests are not controlled with the available Cry proteins. It is also important to provide alternatives to address the problem of insect resistance, which has already appeared with the use of formulations and with transgenic plants that express cry genes that code for insecticidal proteins.

Cardiac ryanodine receptor calcium release deficiency syndrome.

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia, a condition characterized by prominent ventricular ectopy in response to catecholamine stress, which can be reproduced on exercise stress testing (EST). However, reports of sudden cardiac death (SCD) have emerged in EST-negative individuals who have loss-of-function (LOF) RyR2 mutations. The clinical relevance of RyR2 LOF mutations including their pathogenic mechanism, diagnosis, and treatment are all unknowns.