Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

Magnetic resonance enterography and intestinal ultrasound for the assessment and monitoring of Crohn’s disease

Magnetic resonance enterography (MRE) and intestinal ultrasound (IUS) have developed rapidly in the last few decades, emerging as the primary non-invasive options for both diagnosing and monitoring Crohn’s disease (CD). In this review, we evaluate the pertinent data relating to the use of MRE and IUS in CD. We summarise the key imaging features of CD activity, highlight their increasing role in both the clinical and research settings, and discuss how these modalities fit within the diagnostic pathway. We discuss how they can be used to assess disease activity and treatment responsiveness, including the emergence of activity scores for standardised reporting. Additionally, we address areas of controversy such as the use of contrast agents, the role of diffusion-weighted imaging, and discuss point-of-care ultrasound. We also highlight exciting new developments including the applications of artificial intelligence. Finally, we provide suggestions for future research priorities

A Rapidly Deployable Test Suite for Respiratory Protective Devices in the COVID-19 Pandemic

Introduction: The current COVID-19 pandemic has caused large shortages in personal protective equipment, leading to hospitals buying their supplies from alternative suppliers or even reusing single-use items. Equipment from these alternative sources first needs to be tested to ensure that they properly protect the clinicians that depend on them. This work demonstrates a test suite for protective face masks that can be realized rapidly and cost effectively, using mainly off-the-shelf as well as 3D printing components. Materials and Methods: The proposed test suite was d

Chlamydia psittaci: a relevant cause of community-acquired pneumonia in two Dutch hospitals.

Of all hospitalised community-acquired pneumonias (CAPs) only a few are known to be caused by Chlamydia psittaci. Most likely the reported incidence, ranging from of 0% to 2.1%, is an underestimation of the real incidence, since detection of psittacosis is frequently not incorporated in the routine microbiological diagnostics in CAP or serological methods are used

Electrical impedance tomography system: an open access circuit design

BACKGROUND: This paper reports a simple 2-D system for electrical impedance tomography EIT, which works efficiently and is low cost. The system has been developed in the Sharif University of Technology Tehran-Iran (for the author's MSc Project). METHODS: The EIT system consists of a PC in which an I/O card is installed with an external current generator, a multiplexer, a power supply and a phantom with an array of electrodes. The measurement system provides 12-bit accuracy and hence, suitable data acquisition software has been prepared accordingly. The synchronous phase detection method has been implemented for voltage measurement. Different methods of image reconstruction have been used with this instrument to generate electrical conductivity images. RESULTS: The results of simulation and real measurement of the system are presented. The reconstruction programs were written in MATLAB and the data acquisition software in C++. The system has been tested with both static and dynamic mode in a 2-D domain. Better results have been produced in the dynamic mode of operation, due to the cancellation of errors. CONCLUSION: In the spirit of open access publication the design details of this simple EIT system are made available here

Putative role of the adenosine A3 receptor in the antiproliferative action of N6-(2-isopentenyl)adenosine

We tested a panel of naturally occurring nucleosides for their affinity towards adenosine receptors. Both N6-(2-isopentenyl)adenosine (IPA) and racemic zeatin riboside were shown to be selective human adenosine A3 receptor (hA3R) ligands with affinities in the high nanomolar range (Ki values of 159 and 649 nM, respectively). These values were comparable to the observed Ki value of adenosine on hA3R, which was 847 nM in the same radioligand binding assay. IPA also bound with micromolar affinity to the rat A3R. In a functional assay in Chinese hamster ovary cells transfected with hA3R, IPA and zeatin riboside inhibited forskolin-induced cAMP formation at micromolar potencies. The effect of IPA could be blocked by the A3R antagonist VUF5574. Both IPA and reference A3R agonist 2-chloro-N6-(3-iodobenzyl)adenosine-5′-N-methylcarboxamide (Cl-IB-MECA) have known antitumor effects. We demonstrated strong and highly similar antiproliferative effects of IPA and Cl-IB-MECA on human and rat tumor cell lines LNCaP and N1S1. Importantly, the antiproliferative effect of low concentrations of IPA on LNCaP cells could be fully blocked by the selective A3R antagonist MRS1523. At higher concentrations, IPA appeared to inhibit cell growth by an A3R-independent mechanism, as was previously reported for other A3R agonists. We used HPLC to investigate the presence of endogenous IPA in rat muscle tissue, but we could not detect the compound. In conclusion, the antiproliferative effects of the naturally occurring nucleoside IPA are at least in part mediated by the A3R