Publications by authors named "Packard C"

Article Synopsis
  • ApoB is the key protein found in LDL and other lipoproteins, playing a major role in their formation and link to atherosclerosis.
  • LDL contributes to plaque formation in arteries by entering the wall and triggering inflammatory responses through interaction with other molecules, leading to harmful processes like foam cell formation.
  • Research has identified potential interventions to combat atherosclerosis by lowering lipoprotein levels and addressing the inflammatory responses in the arterial wall.
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The properties of tissue interfaces - between separate populations of cells, or between a group of cells and its environment - has attracted intense theoretical, computational, and experimental study. Recent work on shape-based models inspired by dense epithelia have suggested a possible "topological sharpening" effect, by which four-fold vertices spatially coordinated along a cellular interface lead to a cusp-like restoring force acting on cells at the interface, which in turn greatly suppresses interfacial fluctuations. We revisit these interfacial fluctuations, focusing on the distinction between short length scale reduction of interfacial fluctuations and long length scale renormalized surface tension.

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Article Synopsis
  • Lipoprotein(a) is a harmful particle that can increase the risk of heart disease and problems with the aortic valve.
  • New studies show that Lp(a) is much more dangerous than LDL, which is another type of fat in the blood.
  • Learning more about Lp(a) is important because it could help doctors figure out who is at risk and how to better treat heart problems.
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Background: Triglyceride-rich lipoproteins and remnants (TRL/remnants) have a causal, but not yet quantified, relationship with coronary heart disease (CHD): myocardial infarction plus revascularization.

Objectives: The authors sought to estimate TRL/remnant per-particle atherogenicity, investigate causal relationships with inflammation, and determine whether differences in the atherogenicity of TRL/remnants and low-density lipoprotein (LDL) impact the causal association of non-high-density lipoprotein cholesterol (non-HDL-C) with CHD.

Methods: Single nucleotide polymorphisms (SNPs) (N = 1,357) identified by genome-wide association in the UK Biobank were ranked into 10 clusters according to the effect on TRL/remnant-C vs LDL-C.

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Cardiovascular (CV) disease is the most common cause of death in Europe. Despite proven benefits, use of lipid-lowering therapy remains suboptimal. Treatment goals are often not achieved, even in patients at high risk with atherosclerotic CV disease (ASCVD).

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Flocking behavior is observed in biological systems from the cellular to superorganismal length scales, and the mechanisms and purposes of this behavior are objects of intense interest. In this paper, we study the collective dynamics of bovine sperm cells in a viscoelastic fluid. These cells appear not to spontaneously flock, but transition into a long-lived flocking phase after being exposed to a transient ordering pulse of fluid flow.

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Aims: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals.

Methods And Results: The updated LIFE-CVD (i.

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Article Synopsis
  • Researchers are exploring a method to lower the cost of III-V solar cells by detaching them from their growth substrate, allowing for the reuse of the substrate to produce multiple cells.
  • The study focuses on smoothing the faceted surfaces left on GaAs(100) substrates after spalling to enable the growth of high-quality solar cells.
  • The smoothing process can be influenced by the choice of epilayer material and the introduction of impurities or dopants, which significantly affect the smoothness and rate of surface improvement.
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Recent advances in human genetics, together with a substantial body of epidemiological, preclinical and clinical trial evidence, strongly support a causal relationship between triglyceride-rich lipoproteins (TRLs) and atherosclerotic cardiovascular disease. Consequently, the secretion and metabolism of TRLs have a significant impact on cardiovascular health. This knowledge underscores the importance of understanding the molecular mechanisms and regulation of very-low-density lipoprotein (VLDL) and chylomicron biogenesis.

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The pressure-induced phase transformations of certain rare earth (RE) orthophosphates have attracted broad interest from geoscience to structural ceramics. Studying these transformations has required Raman spectroscopy or synchrotron X-ray diffraction (XRD), each of which suffers from poor signal or limited accessibility, respectively. This study exploits the photoluminescence (PL) of Tb ions and the unique sensitivity of PL to the local bonding environment to interrogate the symmetry-reducing xenotime-monazite phase transformation of TbPO.

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Background: Lipoprotein(a) (Lp(a)) is recognized as a causal factor for coronary heart disease (CHD) but its atherogenicity relative to that of low-density lipoprotein (LDL) on a per-particle basis is indeterminate.

Objectives: The authors addressed this issue in a genetic analysis based on the fact that Lp(a) and LDL both contain 1 apolipoprotein B (apoB) per particle.

Methods: Genome-wide association studies using the UK Biobank population identified 2 clusters of single nucleotide polymorphisms: one comprising 107 variants linked to Lp(a) mass concentration, the other with 143 variants linked to LDL concentration.

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Article Synopsis
  • The use of drugs to lower LDL cholesterol (LDL-C) has significantly decreased the risk of heart disease, but some cardiovascular risk remains.
  • Elevated triglycerides (TGs) and TG-rich lipoproteins are linked to increased cardiovascular risk, highlighting the need to address these factors.
  • New treatments targeting apolipoprotein C-III (apoC-III), which plays a crucial role in TG metabolism, show promise in further reducing triglyceride levels and associated heart disease risk.
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Aims/hypothesis: This study explored the hypothesis that significant abnormalities in the metabolism of intestinally derived lipoproteins are present in individuals with type 2 diabetes on statin therapy. These abnormalities may contribute to residual CVD risk.

Methods: To investigate the kinetics of ApoB-48- and ApoB-100-containing lipoproteins, we performed a secondary analysis of 11 overweight/obese individuals with type 2 diabetes who were treated with lifestyle counselling and on a stable dose of metformin who were from an earlier clinical study, and compared these with 11 control participants frequency-matched for age, BMI and sex.

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Aims: The strength of the relationship of triglyceride-rich lipoproteins (TRL) with risk of coronary heart disease (CHD) compared with low-density lipoprotein (LDL) is yet to be resolved.

Methods And Results: Single-nucleotide polymorphisms (SNPs) associated with TRL/remnant cholesterol (TRL/remnant-C) and LDL cholesterol (LDL-C) were identified in the UK Biobank population. In a multivariable Mendelian randomization analysis, TRL/remnant-C was strongly and independently associated with CHD in a model adjusted for apolipoprotein B (apoB).

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BackgroundApolipoprotein C-III (apoC-III) is a regulator of triglyceride (TG) metabolism, and due to its association with risk of cardiovascular disease, is an emergent target for pharmacological intervention. The impact of substantially lowering apoC-III on lipoprotein metabolism is not clear.MethodsWe investigated the kinetics of apolipoproteins B48 and B100 (apoB48 and apoB100) in chylomicrons, VLDL1, VLDL2, IDL, and LDL in patients heterozygous for a loss-of-function (LOF) mutation in the APOC3 gene.

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Objective: Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL.

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Article Synopsis
  • Recent evidence suggests that triglyceride-rich lipoproteins and their cholesterol remnants contribute significantly to the development of atherosclerosis, a condition leading to cardiovascular disease.
  • Genetic studies show a clear link between high plasma triglyceride levels and increased cardiovascular risk, pointing to key proteins that manage triglyceride transport.
  • Ongoing research aims to uncover the effects of dietary choices and genetic factors on triglyceride regulation, paving the way for targeted therapies that could improve treatment outcomes in patients with high triglyceride levels and related health issues.
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Purpose Of Review: Implementation of intensive LDL cholesterol (LDL-C) lowering strategies and recognition of the role of triglyceride-rich lipoproteins (TRL) in atherosclerosis has prompted re-evaluation of the suitability of current lipid profile measurements for future clinical practice.

Recent Findings: At low concentrations of LDL-C (< 1.8 mmol/l/70 mg/dl), the Friedewald equation yields estimates with substantial negative bias.

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Research has revealed how antiviolence activism can become entangled with the state's punitive agenda, leading to what some have called "carceral feminism." However, this scholarship focuses primarily on the U.S.

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Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD).

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Article Synopsis
  • The PNPLA3-148M variant is linked to higher liver fat but its effect on triglyceride-rich lipoprotein metabolism is unclear.
  • In a study comparing homozygous PNPLA3-148M subjects to controls, researchers found liver fat levels were over three times higher in the PNPLA3-148M group.
  • Despite the increased liver fat, the production rates of triglycerides and apoB100 in VLDL were similar between the two groups, indicating that VLDL production was not affected by the PNPLA3 variant.
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Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of coronary heart disease and stroke. Guidelines for the management of dyslipidaemia from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were updated in late 2019 in light of recent intervention trials involving the use of innovative lipid-lowering agents in combination with statins. The new guidelines advocate achieving very low LDL-C levels in individuals at highest risk, within the paradigm of 'lower is better'.

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Following the neutral results of the dal-OUTCOMES trial, a genome-wide study identified the rs1967309 variant in the adenylate cyclase type 9 () gene on chromosome 16 as being associated with the risk of future cardiovascular events only in subjects taking dalcetrapib, a CETP (cholesterol ester transfer protein) modulator. Homozygotes for the minor A allele (AA) were protected from recurrent cardiovascular events when treated with dalcetrapib, while homozygotes for the major G allele (GG) had increased risk. Here, we present the current state of knowledge regarding the impact of rs1967309 in on clinical observations and biomarkers in dalcetrapib trials and the effects of mouse gene inactivation on cardiovascular physiology.

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