WLB-87848, a Selective σ Receptor Agonist, with an Unusually Positioned NH Group as Positive Ionizable Moiety and Showing Neuroprotective Activity.

The synthesis and pharmacological activity of a new series of thieno[2,3-]pyrimidin-4(3)-one derivatives as sigma-1 receptor (σR) ligands are reported. A hit from a high-throughput screening program was evolved into a highly potent and selective σR agonist () that contains a free NH group as positive ionizable moiety, not fulfilling the usual pharmacophoric features of the σR. The compound shows good physicochemical and ADMET characteristics, displays an agonist profile in the binding immunoglobulin protein/σR association assay, induces neuron viability in an in vitro model of β-amyloid peptide intoxication, and presents positive results against recognition memory impairment induced by hippocampal injection of Aβ peptide in rats after oral treatment, altogether making (WLB-87848) an interesting candidate for neuroprotection.

Discovery of WLB-89462, a New Drug-like and Highly Selective σ Receptor Ligand with Neuroprotective Properties.

The synthesis and pharmacological activity of a new series of isoxazolylpyrimidines as sigma-2 receptor (σR) ligands are reported. Modification of a new hit retrieved in an HTS campaign allowed the identification of the compound WLB-89462 () with good σR affinity ( = 13 nM) and high selectivity vs both the σR ( = 1777 nM) and a general panel of 180 targets. It represents one of the first σR ligands with drug-like properties, linked to a good physicochemical and ADMET profile (good solubility, no CYP inhibition, good metabolic stability, high permeability, brain penetration, and high oral exposure in rodents).

"Domestic Drama," "Love Killing," or "Murder": Does the Framing of Femicides Affect Readers' Emotional and Cognitive Responses to the Crime?

We conducted two framing experiments to test how downplaying femicide frames affect readers' reactions. Results of Study 1 (Germany,  = 158) indicate that emotional reactions were increased when a femicide was labeled as "murder" compared to "domestic drama." This effect was strongest among individuals with high hostile sexism.

Lipidomic analysis of surfactant and plasma from horses with asthma and age-matched healthy horses.

Objective: To perform lipidomic analysis of surfactant and plasma from asthmatic and healthy horses.

Animals: 30 horses with clinical signs of asthma and 30 age-matched control horses.

Procedures: Detailed history, physical examination, CBC, and bronchoalveolar lavage fluid (BALF) cytologies were obtained.

"It's a war! It's a battle! It's a fight!": Do militaristic metaphors increase people's threat perceptions and support for COVID-19 policies?

At the beginning of the COVID-19 pandemic, governments around the world employed militaristic metaphors to draw attention to the dangers of the virus. But, do militaristic metaphors truly affect individuals' perceived threat of the COVID-19 virus and increase their support for corresponding restrictive policies? This study assessed the effects of fictitious newspaper articles that described COVID-19 policies using similarly negatively valenced metaphors but with differing militaristic connotations (e.g.

Propionamide Derivatives as Dual μ-Opioid Receptor Agonists and σ Receptor Antagonists for the Treatment of Pain.

A new series of propionamide derivatives was developed as dual μ-opioid receptor agonists and σ receptor antagonists. Modification of a high-throughput screening hit originated a series of piperazinylcycloalkylmethyl propionamides, which were explored to overcome the challenge of achieving balanced dual activity and convenient drug-like properties. The lead compound identified, , showed good analgesic effects in several animal models of both acute (paw pressure) and chronic (partial sciatic nerve ligation) pain, with reduced gastrointestinal effects in comparison with oxycodone.

Dynamics of DHA and EPA supplementation: incorporation into equine plasma, synovial fluid, and surfactant glycerophosphocholines.

Introduction: Horses with asthma or osteoarthritis frequently receive ω-3 fatty acid supplements. Docosahexaenoic (DHA; 22:6) and eicosapentaenoic (EPA; 20:5) acids are essential ω-3 fatty acid precursors of anti-inflammatory mediators and components of structural glycerophospholipids (GPL) that act as reservoirs of these fatty acids. Analysis of the incorporation of dietary DHA + EPA into GPL pools in different body compartments has not been undertaken in horses.

Lipidomics of the chicken egg yolk: high-resolution mass spectrometric characterization of nutritional lipid families.

While previous studies have characterized the fatty acids and global lipid families of the chicken egg yolk, there have been no publications characterizing the individual lipids in these lipid families. Such an in-depth characterization of egg yolk lipids is essential to define the potential benefits of egg yolk consumption for the supply of structural and anti-inflammatory lipids. Historically, the major focus has been on the cholesterol content of eggs and the potential negative health benefits of this lipid, while ignoring the essential roles of cholesterol in membranes and as a precursor to other essential sterols.

Surfactant protein D concentrations in serum and bronchoalveolar lavage fluid from young healthy horses on pasture and in a barn environment.

Objective: To evaluate surfactant protein D (SP-D) concentrations in serum and bronchoalveolar lavage fluid (BALF) from young healthy horses on pasture or housed in a typical barn.

Animals: 20 young healthy horses.

Procedures: Horses were randomly assigned to 1 of 2 groups (pasture, n = 10; barn, 10), and serum and BALF samples were collected for SP-D determination at baseline (all horses on pasture) and 2 weeks and 4 weeks after the barn group of horses was relocated from the pasture to the barn.

Best practices in veterinary personal protective equipment.

Personal protective equipment (PPE) is used every day in veterinary practice. In the context of infectious disease control, PPE functions as a barrier against disease transmission and spread. It is selected based on a disease risk assessment and the circumstances in which it is to be used.

Evidence of Leptospiral Presence in the Cumberland Gap Region.

Background: Leptospirosis is a widespread zoonotic disease that causes reproductive losses and/or hepatorenal failure in a number of animal species. Wild reservoirs of the disease, such as rodents, harbor the causative bacterium, Leptospira spp., in their kidneys and contaminate the environment by excreting infected urine.

Evaluation of lipid markers in surfactant obtained from asthmatic horses exposed to hay.

OBJECTIVE To evaluate the lipidomic profile of surfactant obtained from horses with asthma at various clinical stages and to compare results with findings for healthy horses exposed to the same conditions. SAMPLE Surfactant samples obtained from 6 horses with severe asthma and 7 healthy horses. PROCEDURES Clinical evaluation of horses and surfactant analysis were performed.

Impact of Context Information on Metaphor Elaboration.

In experiments by Gibbs, Kushner, and Mills (1991) , sentences were supposedly either authored by poets or by a computer. Gibbs et al. (1991) concluded from their results that the assumed source of the text influences speed of processing, with a higher speed for metaphorical sentences in the Poet condition.

Effect of Different Instructional Methods on Contamination and Personal Protective Equipment Protocol Adherence among Veterinary Students.

Proper use of personal protective equipment (PPE) is crucial to prevent disease spread. Recent studies in human medicine have shown disconcerting inconsistencies in the use of PPE in hospital wards. In this study, we compared the effect of three instructional methods for PPE use on contamination and protocol adherence among veterinary students.

Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses.

Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp.

A German-language replication study analysing the role of figurative speech in reasoning.

According to the metaphorical framing model, the use of metaphors in discussing an issue influences recipients' understanding and assessment of that issue. In a recent study, participants read a text referring to a city's crime problem either as a beast or a virus and then proposed counter-measures for that problem. Participants' suggestions differed depending on the metaphor they had read.

Development and Validation of a Model for Training Equine Phlebotomy and Intramuscular Injection Skills.

Simulation in veterinary education offers a solution for bridging the gap between observation and performance of clinical skills. An equine neck model was created that allows repetitive practice of jugular phlebotomy, intramuscular (IM) injection, and intravenous catheterization. The aim of this study was to validate the model for jugular phlebotomy and IM injection.

Effectiveness of a new dietetic weight management food to achieve weight loss in client-owned obese cats.

Objectives: The aim of the study was to evaluate weight loss and maintenance parameters in cats fed a novel weight management food and to assess the owner's perception of the cat's quality of life.

Methods: This study was designed as a prospective, uncontrolled/unmasked clinical trial. One hundred and thirty-two overweight/obese, otherwise healthy, client-owned cats were enrolled.

Synthesis and structure-activity relationship study of a new series of selective σ(1) receptor ligands for the treatment of pain: 4-aminotriazoles.

The synthesis and pharmacological activity of a new series of 4-aminotriazoles as potent σ1 receptor (σ1R) ligands are reported. The compounds were prepared using a 4-5-step process, involving as a key step a click chemistry reaction between ynamides and azides. The most active compounds exhibited nanomolar potency for the σ1R, and the selectivity over the σ2R was improved on decreasing the central amine basicity.

Synthesis and biological evaluation of a new series of hexahydro-2H-pyrano[3,2-c]quinolines as novel selective σ1 receptor ligands.

The synthesis and pharmacological activity of a new series of hexahydro-2H-pyrano[3,2-c]quinoline derivatives as potent σ1 receptor (σ1R) ligands are reported. This family, which does not contain the highly basic amino group usually present in other σ1R ligands, showed high selectivity over the σ2 receptor (σ2R). The activity was shown to reside in only one of the four possible diastereoisomers, which exhibited a perfect match with known σ1R pharmacophores.

Studies on the amination of aryl chlorides with a monoligated palladium catalyst: kinetic evidence for a cooperative mechanism.

Combined spectroscopic, crystallographic, and kinetic studies of the mechanism of aromatic amination with the efficient dinuclear Pd precatalyst [Pd(2)Cl(μ-Cl)PtBu(2)(Bph-Me)] (Bph-Me = 2'-methyl-[1,1'-biphenyl]-2-yl) have revealed overlapping, yet cooperative, mechanistic scenarios, the relative weights of which are strongly influenced by the products formed as the reaction proceeds. The stability and evolution of the precatalyst in solution has been studied and several metalation pathways that point to a single monoligated intermediate have been identified. Our work sheds light on the nature of the catalytic species involved in the process and on the structure of the corresponding catalytic network.

Synthesis and biological evaluation of the 1-arylpyrazole class of σ(1) receptor antagonists: identification of 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862).

The synthesis and pharmacological activity of a new series of 1-arylpyrazoles as potent σ(1) receptor (σ(1)R) antagonists are reported. The new compounds were evaluated in vitro in human σ(1)R and guinea pig σ(2) receptor (σ(2)R) binding assays. The nature of the pyrazole substituents was crucial for activity, and a basic amine was shown to be necessary, in accordance with known receptor pharmacophores.

Voice modulations in German ironic speech.

Previous research has shown that in different languages ironic speech is acoustically modulated compared to literal speech,and these modulations are assumed to aid the listener in the comprehension process by acting as cues that mark utterances as ironic. The present study was conducted to identify paraverbal features of German 'ironic criticism' that may possibly act as irony cues by comparing acoustic measures of ironic and literal speech. For this purpose, samples of scripted ironic and literal target utterances produced by 14 female speakers were recorded and acoustically analyzed.

Serum concentration of surfactant protein D in horses with lower airway inflammation.

Reasons For Performing Study: Surfactant protein D (SP-D), mainly synthesised by alveolar type II cells and nonciliated bronchiolar cells, is one important component of innate pulmonary immunity. In man, circulating concentrations of SP-D are routinely used as biomarkers for pulmonary injury. To date, serum SP-D levels have only been investigated in horses in an experimental model of bacterial airway infection.