Synthesis, Analytical Characterization, and Human CB Receptor Binding Studies of the Chloroindole Analogues of the Synthetic Cannabinoid MDMB-CHMICA.

Synthetic cannabinoids (SCs) are one of the largest groups of new psychoactive substances (NPSs). However, the relationship between their chemical structure and the affinity to human CB receptors (hCB), which mediates their psychotropic activity, is not well understood. Herein, the synthesis of the 2-, 4-, 5-, 6- and 7-chloroindole analogues of the synthetic cannabimimetic MDMB-CHMICA, along with their analytical characterization via ultraviolet-visible (UV/VIS), infrared (IR), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry, is described.

Hemodynamic Assay of Hind Limb in Multiple Animal Models.

Introduction: Measuring hemodynamic characteristics of injured limbs is paramount to early identification of potentially damaging ischemic conditions, but can often prove difficult attributable to a multitude of factors. Here, we present an in vivo optical imaging technique to characterize pulsatile blood flow quality through the distal extremity in multiple animal models that replicate the signs of distal extremity ischemia. The purpose of this study is to examine the feasibility of the optical imaging technique and relevance to hemodynamic complications such as acute compartment syndrome (ACS) and nonobvious hemorrhage.

Understanding the Attachment Dimension of Human-animal Bond within A Homeless Population: A One-Health Initiative in the Student Health Outreach for Wellness (SHOW) Clinic.

In response to a gap in veterinary care for low-income, under-served populations, the Student Health Outreach for Wellness (SHOW) Clinic in Phoenix, AZ took a One-Health initiative to establish a pilot veterinary care program to serve the veterinary needs of the local homeless pet owners receiving human medical care at the clinic. The study examines the pilot program through the lens of the human-animal bond (HAB) and focuses specifically on the attachment dimension of the bond as measured by the Lexington Attachment to Pets Scale (LAPS). Data was collected from the homeless pet owners, and Rasch modeling was used to investigate the importance of various factors of the owner attachment to pet as described in LAPS items.

Modelling the N400 brain potential as change in a probabilistic representation of meaning.

The N400 component of the event-related brain potential has aroused much interest because it is thought to provide an online measure of meaning processing in the brain. However, the underlying process remains incompletely understood and actively debated. Here we present a computationally explicit account of this process and the emerging representation of sentence meaning.

Chemical profiling of the synthetic cannabinoid MDMB-CHMICA: Identification, assessment, and stability study of synthesis-related impurities in seized and synthesized samples.

In this work, the most discriminating synthesis-related impurities found in samples from seizures and controlled synthesis of the synthetic cannabinoid MDMB-CHMICA (methyl (S)-2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate) were characterized. Based on 61 available powder samples of MDMB-CHMICA, 15 key-impurities were assessed, isolated in larger quantities via flash chromatography and structurally elucidated and characterized via high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Apart from verifying the relation of the impurities to the major component, the interpretation of their chemical structures with distinct structural elements provided first insights into the manufacturing process and the precursor compounds used.

Building on prior knowledge without building it in.

Lake et al. propose that people rely on "start-up software," "causal models," and "intuitive theories" built using compositional representations to learn new tasks more efficiently than some deep neural network models. We highlight the many drawbacks of a commitment to compositional representations and describe our continuing effort to explore how the ability to build on prior knowledge and to learn new tasks efficiently could arise through learning in deep neural networks.

Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D.

A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.

Synthesis of Lamellarin D Trimethyl Ether and Lamellarin H via 6π-Electrocyclization.

An electrocyclic ring closure of a 2-azapentadienyl anion generated in situ from a chalcone and glycine ester is the key step of an efficient synthesis of the pyrrole core of the lamellarin alkaloids. A recently developed scalable one-pot procedure provides multigram quantities of a 3,5-diaryl-4-iodopyrrole-2-carboxylate intermediate which is transformed in four further high-yielding operations including a one-pot Pomeranz-Fritsch alkylation/cyclization and an Ullmann-type lactone ring closure into the pentacyclic lamellarin skeleton.

Effectiveness and adverse effects of the use of apomorphine and 3% hydrogen peroxide solution to induce emesis in dogs.

Objective: To determine the effectiveness and adverse effects of apomorphine and 3% hydrogen peroxide solution used for emesis in dogs.

Design: Prospective observational study.

Animals: 147 dogs that received apomorphine (IV or placed in the conjunctival sac) or 3% hydrogen peroxide solution (PO) to induce emesis after exposure to toxic agents.

Toxicokinetic profile of N-(2-aminoethyl)ethanolamine in the female Wistar rat and distribution into the late gestation fetus and milk.

N-(2-aminoethyl)ethanolamine (AEEA) caused aneurysms of the great vessels in rats exposed in utero and during the first days post partum, exacerbated by postnatal treatment of the lactating dams (Moore et al., 2012). The purpose of this work was to examine the systemic availability of AEEA during gestation and early lactation.

An overview of trends in animal poisoning cases in the United States: 2002-2010.

Veterinary toxicology is a constantly evolving field. The authors use the ASPCA Animal Poison Control Center’s medical record database to examine recent trends in veterinary toxicology/animal poisoning incidents received from 2002 to 2010. The demographics of animals exposed to potentially harmful substances, the types of substances ingested, changes/emerging trends in substance exposures, and trends in therapies used to treat exposures are discussed.

Carrier-mediated electrodialysis.

Supported liquid membranes containing valinomycin or a calix[4]arene carrier can support electrodialysis under an imposed transmembrane potential. Under optimal conditions both transmembrane flux and carrier-based cation selectivity are enhanced relative to simple dialysis mediated by the same carriers.

Assessment of targeting accuracy of a low-energy stereotactic radiosurgery treatment for age-related macular degeneration.

Age-related macular degeneration (AMD), a leading cause of blindness in the United States, is a neovascular disease that may be controlled with radiation therapy. Early patient outcomes of external beam radiotherapy, however, have been mixed. Recently, a novel multimodality treatment was developed, comprising external beam radiotherapy and concomitant treatment with a vascular endothelial growth factor inhibitor.

Kilovoltage stereotactic radiosurgery for age-related macular degeneration: assessment of optic nerve dose and patient effective dose.

Age-related macular degeneration (AMD) is a leading cause for vision loss for people over the age of 65 in the United States and a major health problem worldwide. Research for new treatments of the wet form of the disease using kilovoltage stereotactic radiosurgery is currently underway at Oraya Therapeutics, Inc. In the present study, the authors extend their previous computational stylized model of a single treated eye [Med.

Dosimetry characterization of a multibeam radiotherapy treatment for age-related macular degeneration.

Age-related macular degeneration (ARMD) is a major health problem worldwide. Advanced ARMD, which ultimately leads to profound vision loss, has dry and wet forms, which account for 20% and 80% of cases involving severe vision loss, respectively. A new device and approach for radiation treatment of ARMD has been recently developed by Oraya Therapeutics, Inc.

The effect of route, vehicle, and divided doses on the pharmacokinetics of chlorpyrifos and its metabolite trichloropyridinol in neonatal Sprague-Dawley rats.

There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single versus divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol, were measured at multiple times through 24 h.

Learning to optimize speed, accuracy, and energy expenditure: a framework for understanding speed-accuracy relations in goal-directed aiming.

Over the last century, investigators have developed a number of models to explain the relation between speed and accuracy in target-directed manual aiming. The models vary in the extent to which they stress the importance of feedforward processes and the online use of sensory information (see D. Elliott, W.

The bioconcentration and metabolism of chlorpyrifos by the eastern oyster, Crassostrea virginica.

Eastern oysters (Crassostrea virginica) were exposed to [14C]chlorpyrifos (O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl] phosphorothioate) at an average measured seawater concentration of 0.6 microg/L under flow-through conditions for 28 d. The compound O,O-diethyl-O-(3,5-dichloro-6-methylthio-2-pyridyl)phosphorothioate (DMP) was extracted and identified as the single metabolite observed, and this metabolite constituted the majority of the total [14C] activity in the oyster at all sampling times.