Delay discounting of money and health outcomes, and adherence to policy guidelines during the COVID-19 pandemic.

Delay discounting refers to the observation that the subjective value of an outcome decreases as the delay to its receipt increases. It is well-established that steep delay discounting is related to various maladaptive behaviors, including poorer health-related choices. One of the current challenges of public health policies that emerged during the COVID-19 pandemic is to encourage preventive behaviors against infectious diseases.

The globalizability of temporal discounting.

Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups.

Tools for public health policy: nudges and boosts as active support of the law in special situations such as the COVID-19 pandemic.

In recent years, "nudging" has become a standard behavioral intervention at the individual level and for the design of social policies. Although nudges are effective, such interventions seem to be limited to a given space and time, and there is only scant evidence to support the contrary view. On the other hand, choice architects may utilize another type of intervention called "boosting," which shows the promise of generalized and lasting behavioral change.

Messaging Protocols for IoT Systems-A Pragmatic Comparison.

There are a dozen messaging protocols proposed for IoT systems. Choosing one for a new design is complicated, and a non-optimal selection can result in slower development and higher design costs. This paper aims to help select appropriate protocols, considering IoT applications' specificity and communication requirements.

Mental Health, Well-Being, and Psychological Flexibility in the Stressful Times of the COVID-19 Pandemic.

This study investigated the relationships between selected emotional aspects of mental ill-health (depression, anxiety, and stress, DASS) and mental well-health (well-being) experienced during the COVID-19 pandemic. The theoretical model of the study was based on Martin Seligman's positive psychology and PERMA theory and Paul Wong's Existential Positive Psychology 2.0 Theory, which postulates that negative experiences contribute to well-being and personal growth.

From Face-to-Face to Facebook: Probing the Effects of Passive Consumption on Interpersonal Attraction.

Social media is radically altering the human social landscape. Before the internet era, human interaction consisted chiefly of direct and reciprocal contact, yet with the rise of social media, the passive consumption of other users' information is becoming an increasingly popular pastime. Passive consumption occurs when a user reads the posts of another user without interacting with them in any way.

In Vivo Functional Evaluation of Tissue-Engineered Vascular Grafts Fabricated Using Human Adipose-Derived Stem Cells from High Cardiovascular Risk Populations.

Many preclinical evaluations of autologous small-diameter tissue-engineered vascular grafts (TEVGs) utilize cells from healthy humans or animals. However, these models hold minimal relevance for clinical translation, as the main targeted demographic is patients at high cardiovascular risk such as individuals with diabetes mellitus or the elderly. Stem cells such as adipose-derived mesenchymal stem cells (AD-MSCs) represent a clinically ideal cell type for TEVGs, as these can be easily and plentifully harvested and offer regenerative potential.

Extracellular matrix fiber microarchitecture is region-specific in bicuspid aortic valve-associated ascending aortopathy.

Objective: Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions.

Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review.

Aortic disease is a significant cause of death in developed countries. The most common forms of aortic disease are aneurysm, dissection, atherosclerotic occlusion and ageing-induced stiffening. The microstructure of the aortic tissue has been studied with great interest, because alteration of the quantity and/or architecture of the connective fibres (elastin and collagen) within the aortic wall, which directly imparts elasticity and strength, can lead to the mechanical and functional changes associated with these conditions.

An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure.

Pulmonary edema resulting from high pulmonary venous pressure (PVP) is a major cause of morbidity and mortality in heart failure (HF) patients, but current treatment options demonstrate substantial limitations. Recent evidence from rodent lungs suggests that PVP-induced edema is driven by activation of pulmonary capillary endothelial transient receptor potential vanilloid 4 (TRPV4) channels. To examine the therapeutic potential of this mechanism, we evaluated TRPV4 expression in human congestive HF lungs and developed small-molecule TRPV4 channel blockers for testing in animal models of HF.

Adult stem cell-based tissue engineered blood vessels: a review.

With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for a small-diameter (<6 mm inner diameter) vascular graft that can provide long-term patency. Tissue engineering provides a very promising solution to this need. Approaches utilizing adult stem cells can address limitations previously realized in the use of terminally differentiated vascular cells, without introducing the ethical concerns that continue to limit the exploration and use of embryonic stem cells.

The discovery of tertiary-amine LXR agonists with potent cholesterol efflux activity in macrophages.

The liver X receptors (LXR) play a key role in cholesterol homeostasis and lipid metabolism. SAR studies around tertiary-amine lead molecule 2, an LXR full agonist, revealed that steric and conformational changes to the acetic acid and propanolamine groups produce dramatic effects on agonist efficacy and potency. The new analogs possess good functional activity, demonstrating the ability to upregulate LXR target genes, as well as promote cholesterol efflux in macrophages.

Modified PAXgene method allows for isolation of high-integrity total RNA from microlitre volumes of mouse whole blood.

Analysis of gene expression is often used to evaluate the effects of experimental manipulations in laboratory animals. Blood is a rich source of potential biomarkers, including gene expression information, which may be obtained from whole blood. When compared with the end of a study, when whole blood samples can be easily obtained for gene expression measurements, the limiting volumes of whole blood obtainable from animals during the course of an experiment requires a method for RNA isolation from a minimal volume of whole blood.

Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors.

Endothelial lipase (EL) activity has been implicated in HDL catabolism, vascular inflammation, and atherogenesis, and inhibitors are therefore expected to be useful for the treatment of cardiovascular disease. Sulfonylfuran urea 1 was identified in a high-throughput screening campaign as a potent and non-selective EL inhibitor. A lead optimization effort was undertaken to improve potency and selectivity, and modifications leading to improved LPL selectivity were identified.

A high-throughput screen for endothelial lipase using HDL as substrate.

Endothelial lipase (EL) is a 482-amino-acid protein from the triglyceride lipase gene family that uses a Ser-His-Asp triad for catalysis. Its expression in endothelial cells and preference for phospholipids rather than triglycerides are unique. Animal models in which it is overexpressed or knocked out indicate EL levels are inversely correlated with high-density lipoprotein cholesterol (HDL-C).

Poloxamer 407 (P-407)-mediated reduction in the gene expression of ATP-binding-cassette transporter A1 may contribute to increased cholesterol in peripheral tissues of P-407-treated rats.

The purpose of this study was to determine whether poloxamer 407, a chemical known to increase plasma lipid levels in rodents following parenteral administration, decreased the gene expression of ATP-binding-cassette transporter A1. Using human macrophages cultured with poloxamer 407, there was a significant reduction in the gene expression of ATP-binding-cassette transporter A1; however, there was no effect on the gene expression of either fatty acid synthase or sterol regulatory element binding protein-1. Reduction of ATP-binding-cassette transporter A1 mRNA levels was also observed in both liver and intestine of poloxamer 407-treated rats.

Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure.

Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 as an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.

Synthetic LXR agonists increase LDL in CETP species.

Liver X receptor (LXR) nuclear receptors regulate the expression of genes involved in whole body cholesterol trafficking, including absorption, excretion, catabolism, and cellular efflux, and possess both anti-inflammatory and antidiabetic actions. Accordingly, LXR is considered an appealing drug target for multiple indications. Synthetic LXR agonists demonstrated inhibition of atherosclerosis progression in murine genetic models; however, these and other studies indicated that their major undesired side effect is an increase of plasma and hepatic triglycerides.

Endothelial lipase and HDL metabolism.

Purpose Of Review: In the past year, several laboratories taking independent approaches have provided compelling evidence that endothelial lipase, a relatively recent addition to the triglyceride lipase gene family, is a major determinant of HDL metabolism. This review summarizes recent findings from experiments in mice with altered levels of endothelial lipase, from an examination of endothelial lipase catalytic and non-catalytic functions in vitro, and from human genetic studies.

Recent Findings: An analysis of lipids and lipoproteins in endothelial lipase knockout and transgenic mice and in mice with adenovirus-driven hepatic overexpression of endothelial lipase shows, without exception, that total cholesterol, phospholipid and HDL-cholesterol all vary inversely with the endothelial lipase gene dosage, and primarily depend on endothelial lipase catalytic activity.

Identification of novel isoform-selective inhibitors within class I histone deacetylases.

Histone deacetylases (HDACs) represent an expanding family of protein modifying-enzymes that play important roles in cell proliferation, chromosome remodeling, and gene transcription. We have previously shown that recombinant human HDAC8 can be expressed in bacteria and retain its catalytic activity. To further explore the catalytic activity of HDACs, we expressed two additional human class I HDACs, HDAC1 and HDAC3, in baculovirus.

A novel endothelial-derived lipase that modulates HDL metabolism.

High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease. At least 50% of the variation in HDL cholesterol levels is genetically determined, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism and the HL (LIPC) locus has been associated with variation in HDL cholesterol levels in humans.

Tyrphostins inhibit PDGF-induced DNA synthesis and associated early events in smooth muscle cells.

Tyrphostins are low-molecular-weight synthetic inhibitors of protein tyrosine kinase, which block cell proliferation. Since platelet-derived growth factor (PDGF) is thought to figure prominently in disorders of vascular smooth muscle cells (VSMC), such as atherosclerosis, hypertension, and restenosis, we examined whether tyrphostins would inhibit PDGF-induced mitogenesis in VSMC. In this communication, we demonstrate that tyrphostins with the benzenemalononitrile nucleus inhibited PDGF-dependent growth of VSMC as well as PDGF-dependent DNA synthesis in these cells, with the concentrations for 50% inhibition ranging from 0.