Expert Opin Pharmacother
December 2024
Introduction: Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies have been performed, but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them.
Areas Covered: Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a).
The PALISADE trial extended the data available for inhibition of apolipoprotein (apo) C3 inhibition for treating severe hypertriglyceridemia. 75 patients with persistent chylomicronemia were allocated to 2 doses of plozasiran or placebo. Triglycerides were reduced by a net 53%-58%, and a borderline significant 17% reduction was seen in pancreatitis events.
View Article and Find Full Text PDFBackground: The risk-benefit balance of statin use in healthy older people is uncertain. We describe the baseline characteristics of the STAREE (Statins in Reducing Events in the Elderly) trial, which is a randomized, double-blind, placebo-controlled trial among community-dwelling older people; the trial evaluated the effect of atorvastatin 40 mg for the prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke), and on disability-free survival (survival free of both dementia and persistent physical disability).
Methods And Results: STAREE enrolled people aged ≥70 years from 1583 general practices across Australia with no history of clinical cardiovascular disease, diabetes, or dementia.
Plastid-encoded RNA polymerase (PEP) is a bacterial-type multisubunit RNA polymerase responsible for the majority of transcription in chloroplasts. PEP consists of four core subunits, which are orthologs of their cyanobacterial counterparts. In Arabidopsis thaliana, PEP is expected to interact with 14 PEP-associated proteins (PAPs), which serve as peripheral subunits of the RNA polymerase.
View Article and Find Full Text PDFBackground: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder. This study aimed to study the genotype distribution of FCS-causing genes in the United Kingdom, genotype-phenotype correlation, and clinical differences between FCS and multifactorial chylomicronemia syndrome (MCS).
Methods: The study included 154 patients (FCS, 74; MCS, 80) from the UK FCS national registry and the UK arm of the FCS International Quality Improvement and Service Evaluation Project.
Familial chylomicronemia syndrome (FCS) is a rare inherited disorder characterized by severe hypertriglyceridemia, posing a heightened risk of acute pancreatitis. Recently, Volanesorsen, an APOC3 antisense oligonucleotide, gained approval for FCS treatment in the UK. Caution is advised during pregnancy due to limited safety data, although animal studies show no toxicity/teratogenicity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
July 2024
DNA is organized into chromatin-like structures that support the maintenance and regulation of genomes. A unique and poorly understood form of DNA organization exists in chloroplasts, which are organelles of endosymbiotic origin responsible for photosynthesis. Chloroplast genomes, together with associated proteins, form membrane-less structures known as nucleoids.
View Article and Find Full Text PDFOver the past two decades, there has been a growing interest in research on aging and the decision-making behavior of older consumers. The subject of this article is multi-attribute decisions made using product comparison, a widely used functionality of many e-commerce stores. Studies on cognitive aging have established a negative relationship between age and accuracy in multi-attribute choice tasks; however, works in informatics (Human-Computer Interaction, UX research) have not accounted for how individual user differences affect the optimality of users' product comparison decisions.
View Article and Find Full Text PDFObjective: Novel lipid-lowering therapies are being introduced. Few studies exist of the real-world effectiveness of adenosine-tri-phosphate citrate lyase inhibition with bempedoic acid.
Methods: This study audited bempedoic acid therapy in 216 consecutive patients from three hospital centres - a university hospital ( = 77) and two district general hospitals ( = 106 and 33).
Background: Although researchers extensively study the rapid generation and spread of misinformation about the novel coronavirus during the pandemic, numerous other health-related topics are contaminating the internet with misinformation that have not received as much attention.
Objective: This study aims to gauge the reach of the most popular medical content on the World Wide Web, extending beyond the confines of the pandemic. We conducted evaluations of subject matter and credibility for the years 2021 and 2022, following the principles of evidence-based medicine with assessments performed by experienced clinicians.
Background And Aims: Prognosis and management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it.
View Article and Find Full Text PDFExpert Rev Cardiovasc Ther
March 2024
Introduction: Older adults form a fast-increasing proportion of the world population. However, gains in increasing quantity of life have not been accompanied by similar gains in quality of life. Older people frequently experience frailty, memory problems, and chronic diseases including cardiovascular disease (CVD) and neurodegenerative diseases.
View Article and Find Full Text PDFBackground And Aims: Differences in the perceived prevalence of familial hypercholesterolemia (FH) by ethnicity are unclear. In this study, we aimed to assess the prevalence, determinants and management of diagnostically-coded FH in an ethnically diverse population in South London.
Methods: A cross-sectional analysis of 40 practices in 332,357 adult patients in Lambeth was undertaken.
Background: Primary dyslipidaemias, including familial hypercholesterolaemia, are underdiagnosed genetic disorders that substantially increase risk for premature coronary artery disease in adults. Early identification of primary dyslipidaemias via lipid clinic referral optimises patient management and enables cascade screening of relatives. Improving the identification of primary dyslipidaemias, and understanding disparities in ascertainment and management, is an NHS priority.
View Article and Find Full Text PDFIn this work, a series of novel boronium-bis(trifluoromethylsulfonyl)imide [TFSI] ionic liquids (IL) are introduced and investigated. The boronium cations were designed with specific structural motifs that delivered improved electrochemical and physical properties, as evaluated through cyclic voltammetry, broadband dielectric spectroscopy, densitometry, thermogravimetric analysis, and differential scanning calorimetry. Boronium cations, which were appended with -alkylpyrrolidinium substituents, exhibited superior physicochemical properties, including high conductivity, low viscosity, and electrochemical windows surpassing 6 V.
View Article and Find Full Text PDFCorrection for 'Unorthodox crystalline drug salts the reaction of amine-containing drugs with CO' by Mohammad Soltani , , 2019, , 13546-13549, https://doi.org/10.1039/C9CC06429J.
View Article and Find Full Text PDFCorrection for 'Tuning the melting point of selected ionic liquids through adjustment of the cation's dipole moment' by Brooks D. Rabideau , , 2020, , 12301-12311, https://doi.org/10.
View Article and Find Full Text PDFPP2A-serine/threonine protein phosphatases function as heterotrimeric holoenzymes, composed of a common scaffold (A-subunit encoded by PPP2R1A/PPP2R1B), a common catalytic (C-subunit encoded by PPP2CA/PPP2CB), and one of many variable regulatory (B) subunits. The site of phosphoprotein phosphatase (PPP) hydrolysis features a bimetal system (M/M), an associated bridge hydroxide [W(OH)], and a highly-conserved core sequence. In the presumptive common mechanism, the phosphoprotein's seryl/threonyl phosphate coordinates the M/M system, W(OH) attacks the central P atom, rupturing the antipodal bond, and simultaneously, a histidine/aspartate tandem protonates the exiting seryl/threonyl alkoxide.
View Article and Find Full Text PDFWe have reviewed the genetic basis of chylomicronaemia, the difference between monogenic and polygenic hypertriglyceridaemia, its effects on pancreatic, cardiovascular, and microvascular complications, and current and potential future pharmacotherapies. Severe hypertriglyceridaemia (TG > 10 mmol/L or 1000 mg/dL) is rare with a prevalence of <1%. It has a complex genetic basis.
View Article and Find Full Text PDFIntroduction: The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD).
View Article and Find Full Text PDFThe periodicity of the mutual position of celestial bodies in the Earth-Moon-Sun system is crucial to the functioning of life on Earth. Biological rhythms affect most of the processes inside organisms, and some can be recorded in skeletal remains, allowing one to reconstruct the cycles that occur in nature deep in time. In the present study, we have used ultra-high-resolution elemental ratio scans of Mg/Ca, Sr/Ca and Mn/Ca from the fossil, ca.
View Article and Find Full Text PDFFighting medical disinformation in the era of the pandemic is an increasingly important problem. Today, automatic systems for assessing the credibility of medical information do not offer sufficient precision, so human supervision and the involvement of medical expert annotators are required. Our work aims to optimize the utilization of medical experts' time.
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