Customizable patterned membranes for cardiac tissue engineering: A model-assisted design method.

Myocardial infarction can cause irreversible damage to the heart muscle, which can lead to heart failure. The difficulty of the treatment mainly arises from the anisotropic behavior of the myocardium fibrous structure. Patches or cardiac restraint devices appear to be a promising approach to post-infarction treatment.

Experimental Analysis of the Influence of Heat Treatments on the Flexibility of NiTi Alloy for Endodontic Instruments Manufacturing.

The flexibility of NiTi based endodontic files is improved by heat treatment, leading to lower risk of failure, ledges, and canal transportation during the preparation of curved root canals. The aim of this study is to investigate and clearly highlight the influence of every parameter of heat treatment on the flexibility of NiTi wires and thus of endodontic instruments. A full factorial Design of Experiment (DoE) and a designed bending-torsion bench following the ISO 3630-1 standard were used for this investigation.

Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations.

Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022.

A Chemical Biology Toolbox Targeting the Intracellular Binding Site of CCR9: Fluorescent Ligands, New Drug Leads and PROTACs.

A conserved intracellular allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors (GPCRs). Starting from vercirnon, an intracellular C-C chemokine receptor type 9 (CCR9) antagonist and previous phase III clinical candidate for the treatment of Crohn's disease, we developed a chemical biology toolbox targeting the IABS of CCR9. We first synthesized a fluorescent ligand enabling equilibrium and kinetic binding studies via NanoBRET as well as fluorescence microscopy.

Bivalent ligands promote endosomal trafficking of the dopamine D3 receptor-neurotensin receptor 1 heterodimer.

Bivalent ligands are composed of two pharmacophores connected by a spacer of variable size. These ligands are able to simultaneously recognize two binding sites, for example in a G protein-coupled receptor heterodimer, resulting in enhanced binding affinity. Taking advantage of previously described heterobivalent dopamine-neurotensin receptor ligands, we demonstrate specific interactions between dopamine D3 (DR) and neurotensin receptor 1 (NTSR1), two receptors with expression in overlapping brain areas that are associated with neuropsychiatric diseases and addiction.

Homobivalent Dopamine D Receptor Ligands Modulate the Dynamic Equilibrium of D Monomers and Homo- and Heterodimers.

Dopamine D receptors (DRs) are major targets in the treatment of psychiatric and neurodegenerative diseases. As with many other G protein-coupled receptors (GPCRs), DRs interact within the cellular membrane, leading to a transient receptor homo- or heterodimerization. These interactions are known to alter ligand binding, signaling, and receptor trafficking.

A Dual Mode Adaptive Basal-Bolus Advisor Based on Reinforcement Learning.

Self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) are commonly used by type 1 diabetes (T1D) patients to measure glucose concentrations. The proposed adaptive basal-bolus algorithm (ABBA) supports inputs from either SMBG or CGM devices to provide personalised suggestions for the daily basal rate and prandial insulin doses on the basis of the patients' glucose level on the previous day. The ABBA is based on reinforcement learning, a type of artificial intelligence, and was validated in silico with an FDA-accepted population of 100 adults under different realistic scenarios lasting three simulated months.

An online knowledge resource and questionnaires as a continuing pharmacy education tool to document reflective learning.

Objective: To assess the use of an electronic knowledge resource to document continuing education activities and reveal educational needs of practicing pharmacists.

Methods: Over a 38-week period, 67 e-mails were sent to 6,500 Canadian Pharmacists Association (CPhA) members. Each e-mail contained a link to an e-Therapeutics+ Highlight, a factual excerpt of selected content from an online drug and therapeutic knowledge resource.

Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products.

In this study, we used an in vitro Caco-2 cell monolayer model to evaluate aqueous extracts of commercial-source goldenseal (Hydrastis canadensis) and milk thistle (Silybum marianum) capsule formulations, their marker phytochemicals (berberine and silibinin, respectively), as well as dillapiol, vinblastine, and the HIV protease inhibitor saquinavir for their ability to modulate CYP3A4 and ABCB1 expression after short-term exposure (48 h). Both upregulation and downregulation of CYP3A4 expression was observed with extracts of varying concentrations of the two natural health products (NHPs). CYP3A4 was highly responsive in our system, showing a strong dose-dependent modulation by the CYP3A4 inhibitor dillapiol (upregulation) and the milk thistle flavonolignan silibinin (downregulation).

Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro.

A 70% ethanol extract of California poppy (Eschscholzia californica) was able to bind to 5-HT(1A) and 5-HT(7) receptors at 100 mug/mL. The subsequent isolation procedure yielded the known alkaloids californidine (1), escholtzine (2), N-methyllaurotetanine (3), caryachine (4), and O-methylcaryachine (5), along with a new pavine alkaloid, 6S,12S-neocaryachine-7-O-methyl ether N-metho salt (7). The structure of 7 was determined by spectroscopic data interpretation, while the absolute stereochemistry was determined by means of circular dichroism.

Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties.

The phytochemistry and biological activity of Scutellaria lateriflora L. (American skullcap) which has been traditionally used as a sedative and to treat various nervous disorders such as anxiety was studied. In vivo animal behaviour trials were performed to test anxiolytic effects in rats orally administered S.

In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products.

Spices, herbal and black teas, and soybean products were analyzed for their capacity to inhibit in vitro metabolism of drug marker substrates by human cytochrome P-450 (CYP) isoforms. Inhibition of drug metabolism was determined using aliquots or infusions from these products in a fluorescence-detection assay. Aliquots and infusions of all natural product categories inhibited 3A4 metabolism to some extent.

Effect of several Chinese natural health products of human cytochrome P450 metabolism.

Purpose: Traditional Chinese medicines (TCM) are believed by many to be safe and used for self-medication without supervision. Although the risk appears to be low, certain TCM have been associated with a number of serious adverse reactions. A preliminary study was undertaken with 12 products using a human cytochrome P450 (CYP450) isozyme assay to determine if these products could affect human drug metabolism.

An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic.

Purpose: Garlic has been used as a flavouring agent, traditional medicine, and functional food to improve physical or mental well-being. Garlic and garlic products generally have been regarded as safe but a number of conflicting reports in the literature and confounding factors make it difficult to unequivocally establish the clinical efficacy and safety of these products either alone or in the presence of therapeutic products. A preliminary study was undertaken with fresh garlic and garlic products using the major cDNA-expressed human cytochrome P-450 isozymes associated with the metabolism of HIV/AIDS drugs, and purified P-glycoprotein (P-gp) cell membranes to ascertain the risk potential for generating interactions with therapeutic products.

An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures.

Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13 related pure plant compounds have been analyzed for their in vitro cytochrome P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate assay. Roughly 75% of the commercial products and 50% of the pure compounds showed significant inhibition of CYP3A4 metabolite formation. For each herbal product and pure compound exhibiting dose-dependency, the inhibition values were used to generate median inhibitory concentration (IC50) curves using linear regression.

SNOP: a method for skeletonization of a fringe pattern along the fringe direction.

A new algorithm for fringe-pattern processing is proposed. It consists of tracing fringes along the fringe direction by searching the local extreme values of brightness distribution in the image. A detailed explanation of this method is given, the parameters and criteria for computerized processing are discussed, and some experimental results for testing the method are presented.

Validation of a new technique for measurement of intracranial pressure with a scintillation counter.

Intracranial pressure sensors and subdural and subgaleal sensing tambours were used to measure the pressure difference between the intracranial and subgaleal spaces in two monkeys. The pressure differential was transmitted to fluid bathing a piston, to which an isotope source (145Pm) was attached. The radiation signal emanating through a fixed collimator was detected transcutaneously by a sodium iodide crystal contained within a photomultiplier tube connected to a scintillation counter.