[Peer support, a vector for transforming psychiatric practices].

Peer support is based on the mirror effect between the peer carer and the person being supported, which is a powerful lever for recovery. Through their work, peer helpers also hold up a mirror to "non-peer" carers. The reflection they see is a litmus test that can lead to changes in care practices, but it can also generate defensive reactions.

Deep learning-based algorithm for lung cancer detection on chest radiographs using the segmentation method.

We developed and validated a deep learning (DL)-based model using the segmentation method and assessed its ability to detect lung cancer on chest radiographs. Chest radiographs for use as a training dataset and a test dataset were collected separately from January 2006 to June 2018 at our hospital. The training dataset was used to train and validate the DL-based model with five-fold cross-validation.

Preclinical Evaluation of the Effects of Trazpiroben (TAK-906), a Novel, Potent Dopamine D/D Receptor Antagonist for the Management of Gastroparesis.

Current therapies for gastroparesis metoclopramide and domperidone carry risks of extrapyramidal symptoms and life-threatening cardiac arrhythmias. Trazpiroben, a novel, potent dopamine D/D receptor antagonist, has low brain permeation and very low affinity for human ether-à-go-go-related gene (hERG) channel inhibition, potentially improving on safety profiles of existing therapies. Trazpiroben demonstrated the following receptor affinities: high for D and D, moderate for D, and minimal for D and D It demonstrated moderate affinity for adrenergic 1B ( ) and 5-hydroxytryptamine (5HT) 2A receptors and low potential for off-target adverse events (AEs).

Incidental cerebral aneurysms detected by a computer-assisted detection system based on artificial intelligence: A case series.

Rationale: Computer-assisted detection (CAD) systems based on artificial intelligence (AI) using convolutional neural network (CNN) have been successfully used for the diagnosis of unruptured cerebral aneurysms in experimental situations. However, it is yet unclear whether CAD systems can detect cerebral aneurysms effectively in real-life clinical situations. This paper describes the diagnostic efficacy of CAD systems for cerebral aneurysms and the types of cerebral aneurysms that they can detect.

Deep Learning for MR Angiography: Automated Detection of Cerebral Aneurysms.

Purpose To develop and evaluate a supportive algorithm using deep learning for detecting cerebral aneurysms at time-of-flight MR angiography to provide a second assessment of images already interpreted by radiologists. Materials and Methods MR images reported by radiologists to contain aneurysms were extracted from four institutions for the period from November 2006 through October 2017. The images were divided into three data sets: training data set, internal test data set, and external test data set.

Effect of tecarfarin, a novel vitamin K epoxide reductase inhibitor, on coagulation in beagle dogs.

Background And Purpose: Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Muscarinic receptors in isolated urinary bladder smooth muscle from different mouse strains.

1. The pharmacological characteristics of muscarinic receptors in male and female mouse urinary bladder smooth muscle from different strains (C57Bl/6, 129/SvJ and hybrid backcross N1F2) were studied. 2.

Effect of YM-44781, YM-44778 and YM-49598, novel tachykinin antagonists, in a drug-induced bladder contraction model.

The radioligand binding profiles and in vivo pharmacological characteristics of YM-44781, YM-44778 and YM-49598, novel non-peptide tachykinin receptor antagonists, were examined and compared to those of FK-888 and GR-159897. Since no functional NK(3) receptors were found in the rat bladder, the emphasis will be on the other two subtypes. YM-44781 and YM-49598 exhibited high binding affinities at NK(2) (pK(i) = 9.

Evaluation of oral ro70-0004/003, an alpha1A-adrenoceptor antagonist, in the treatment of male erectile dysfunction.

Alpha-adrenoceptor antagonists have been used for the treatment of male erectile dysfunction (MED). Ro70-0004/003 (Ro70-0004) is a selective and orally active alpha1A-adrenoceptor antagonist. The objective of this study was to: (1) pharmacologically elucidate the alpha1-adrenoceptor subtype mediating norepinephrine-induced contraction of human isolated corpus cavernosal tissue and (2) conduct a clinical proof-of-concept study with Ro70-0004 to test the hypothesis that selective alpha1A-adrenoceptor blockade would improve erectile function in patients with MED.

Pharmacological characterization of muscarinic receptors in mouse isolated urinary bladder smooth muscle.

The pharmacological characteristics of muscarinic receptors in the male mice urinary bladder smooth muscle were studied. (+)-Cis-dioxolane, oxotremorine-M, acetylcholine, carbachol and pilocarpine induced concentration-dependent contractions of the urinary bladder smooth muscle (pEC(50)=6.6+/-0.

Therapeutic opportunities from muscarinic receptor research.

Muscarinic acetylcholine receptor subtypes have been the subjects of research for at least a quarter of a century. Nonetheless, there are few selective muscarinic receptor ligands presently used as therapeutics. The extensive development of muscarinic M(1) receptor agonists for the treatment of cognitive dysfunction has culminated in a series of unsuccessful drug candidates, which reflects a lack of understanding of the disease and the role played by muscarinic cholinergic transmission.

Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle.

1. The pharmacological characteristics of muscarinic receptors mediating contraction of dog isolated ciliary muscle were determined and compared to those mediating contraction of dog urinary bladder smooth muscle. 2.

Characterization of the muscarinic receptor in isolated uterus of sham operated and ovariectomized rats.

1. The pharmacological characteristics of muscarinic receptors in rat isolated uterus were studied in ovariectomized (ov.) and sham operated (sh.

Muscarinic receptor ligands and their therapeutic potential.

Over the past year, the introduction of novel ligands has accelerated the classification of muscarinic receptor subtypes and has led to a better understanding of their physiological role. Important in this respect is the recent recognition of the exquisite selectivity of a series of snake toxins, enabling better definition of the muscarinic subtype 4 receptor. Moreover, several compounds, both agonists and antagonists, are progressing in advanced clinical trials for the treatment of several conditions, including Alzheimer's disease, pain, urinary incontinence and chronic obstructive pulmonary disease.

Characterization of an atypical muscarinic cholinoceptor mediating contraction of the guinea-pig isolated uterus.

In many smooth muscle tissues a minor M3-muscarinic acetylcholine (mACh) receptor population mediates contraction, despite the presence of a larger M2-mACh receptor population. However, this is not the case for guinea-pig uterus where radioligand binding and functional studies exclude a dominant role for M3-mACh receptors. Using tissue from animals pre-treated with diethylstilboestrol, estimates of antagonist affinity were made before and after selective alkylation procedures, together with estimates of agonist affinity to characterise the mACh receptor population mediating carbachol-induced contraction of guinea-pig isolated uterus.

Pharmacological characterization of muscarinic receptors in rabbit isolated iris sphincter muscle and urinary bladder smooth muscle.

1. The pharmacological characteristics of muscarinic receptors in the rabbit iris sphincter muscle were studied and compared to M3 receptors in rabbit urinary bladder smooth muscle. 2.

Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo.

1. Urinary bladder smooth muscle is enriched with muscarinic receptors, the majority of which are of the M2 subtype whereas the remaining minority belong to the M3 subtype. The objective of the present study was to assess the functional role of M2 and M3 receptors in the urinary bladder of rat in vitro and in vivo by use of key discriminatory antagonists.

Influence of vascular tone on vasoconstrictor responses to the 5-HT 1-like receptor agonist sumatriptan in anaesthetised rabbits.

The cardiovascular profile of the 5-HT1-like receptor agonist sumatriptan has been studied in anaesthetised rabbits pretreated with chlorisondamine (0.5 mg kg-1 i.v.

Peripheral benzodiazepine ligands inhibit aggregation and thromboxane synthesis induced by arachidonic acid in rabbit platelets in vitro.

Seven compounds having varying affinities for peripheral benzodiazepine (p sites) were evaluated in vitro as inhibitors of arachidonic acid-induced rabbit platelet aggregation and thromboxane B2 (TXB2) synthesis. With the exception of flumazenil, all compounds inhibited both parameters with IC50 values ranging from 0.19 to 3.

Presence of vasoconstrictor 5HT1-like receptors revealed by precontraction of rabbit isolated mesenteric artery.

1. A series of 5-hydroxytryptamine (5-HT) receptor agonists including 5-HT, 5-carboxamidotryptamine (5-CT) and sumatriptan produced little or no contraction of rabbit isolated mesenteric arteries under resting tone conditions, even at concentrations up to 10(-4) M. 2.

5-Hydroxytryptamine1D-like receptors mediate contraction of partially depolarized rabbit renal arteries.

This study characterizes the 5-hydroxytryptamine (5-HT) receptors involved in the contraction of rabbit renal arteries which had been previously precontracted submaximally by partial depolarization. In the presence of ketanserin (10(-6) M) to block 5-HT2 receptors, 5-HT, 5-carboxamido-tryptamine (5-CT) and other 5-HT receptor agonists caused contraction of partially depolarized (22 mM KCl) rabbit renal arteries whereas they were without effect in quiescent tissues (4.7 mM KCl).

Pre-contraction with histamine and U46619 unmasks a 5-HT1-like receptor in rabbit renal artery.

Rabbit renal arteries were virtually unresponsive to 5-hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) under control conditions (including the presence of ketanserin 10(-6) M). However, both agents produced prominent contractions over the range 10(-9)-10(-5) M in tissues pre-contracted with threshold concentrations of either histamine or U46619. These responses were considered to be mediated by activation of 5-HT1-like receptors based on the potency order 5-CT > or = 5-HT and the sensitivity of agonist responses to antagonism by methiothepin (10(-7) M).

Adsorption studies in a synthetic rubber latex-ovalbumin system.

1. Adsorption of ovalbumin on the latex surface was in excess of the quantity required to produce coverage of the surface over most of the protein concentrations range which was investigated. 2.