2D-to-3D image translation of complex nanoporous volumes using generative networks.

Image-based characterization offers a powerful approach to studying geological porous media at the nanoscale and images are critical to understanding reactive transport mechanisms in reservoirs relevant to energy and sustainability technologies such as carbon sequestration, subsurface hydrogen storage, and natural gas recovery. Nanoimaging presents a trade off, however, between higher-contrast sample-destructive and lower-contrast sample-preserving imaging modalities. Furthermore, high-contrast imaging modalities often acquire only 2D images, while 3D volumes are needed to characterize fully a source rock sample.

Determining pharmacological selectivity of the kappa opioid receptor antagonist LY2456302 using pupillometry as a translational biomarker in rat and human.

Background: Selective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression. The kappa opioid receptor antagonist, LY2456302, exhibits ~30-fold higher affinity for kappa opioid receptors over mu opioid receptors, which is the next closest identified pharmacology.

Methods: Here, we determined kappa opioid receptor pharmacological selectivity of LY2456302 by assessing mu opioid receptor antagonism using translational pupillometry in rats and humans.

LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders.

Kappa opioid receptors and their endogenous neuropeptide ligand, dynorphin A, are densely localized in limbic and cortical areas comprising the brain reward system, and appear to play a key role in modulating stress and mood. Growing literature indicates that kappa receptor antagonists may be beneficial in the treatment of mood and addictive disorders. However, existing literature on kappa receptor antagonists has used extensively JDTic and nor-BNI which exhibit long-lasting pharmacokinetic properties that complicate experimental design and interpretation of results.

Mice lacking δ-opioid receptors resist the development of diet-induced obesity.

Pharmacological manipulation of opioid receptors alters feeding behavior. However, the individual contributions of each opioid receptor subtype on energy balance remain largely unknown. Herein, we investigated whether genetic disruption of the δ-opioid receptor (DOR) also controls energy homeostasis.

A comparison of HIV detection rates using routine opt-out provider-initiated HIV testing and counseling versus a standard of care approach in a rural African setting.

Background: Routine opt-out provider-initiated HIV testing and counseling (PITC) remains underutilized in sub-Saharan Africa. By selectively targeting clients who either volunteer or have clinical indications of HIV disease, standard approaches to HIV counseling and testing are presumed more cost-efficient than PITC.

Methods: One thousand two hundred twenty-one patients aged 15– 49 years were seen by 22 practitioners in a mobile clinic in southern Zambia.

kappa-Opioid receptors control the metabolic response to a high-energy diet in mice.

General opioid receptor antagonists reduce food intake and body weight in rodents, but the contributions of specific receptor subtypes are unknown. We examined whether genetic deletion of the kappa-opioid receptor (KOR) in mice alters metabolic physiology. KOR-knockout (KO) and wild-type (WT) mice were fed a high-energy diet (HED) for 16 wk.

Structure activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 2.

A series of 6-bicycloaryloxynicotinamides were identified as opioid receptor antagonists at mu, kappa, and delta receptors. Compounds in the 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide scaffold exhibited potent in vitro functional antagonism at all three receptors.

In vivo rat brain opioid receptor binding of LY255582 assessed with a novel method using LC/MS/MS and the administration of three tracers simultaneously.

LY255582 is a pan opioid selective receptor antagonist that has been shown to have high affinity for mu, delta, and kappa receptors in vitro. In order to better understand the in vivo opioid receptor selectivity of LY255582, we developed in vivo receptor occupancy assays in the rat for the opioid mu, kappa and delta receptors using the occupancy tracers naltrexone, GR103545 and naltriben respectively. Individual assays for each target were established and then a "triple tracer" assay was created where all three tracers were injected simultaneously, taking advantage of LC/MS/MS technology to selectively monitor brain tracer levels.

Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1.

A structurally unique and new class of opioid receptor antagonists (OpRAs) that bear no structural resemblance with morphine or endogenous opioid peptides has been discovered. A series of carboxamido-biaryl ethers were identified as potent receptor antagonists against mu, kappa and delta opioid receptors. The structure-activity relationship indicated para-substituted aryloxyaryl primary carboxamide bearing an amine tether on the distal phenyl ring was optimal for potent in vitro functional antagonism against three opioid receptor subtypes.

SAR and biological evaluation of novel trans-3,4-dimethyl-4-arylpiperidine derivatives as opioid antagonists.

The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. We have developed a SAR study around LY255582 by comparing the effect of the hydroxy group in the 2- and 4-position of the phenyl ring. Also, we have proved that the 3-position of the phenyl ring is optimal for opioid activity.

Na+ modulation, inverse agonism, and anorectic potency of 4-phenylpiperidine opioid antagonists.

Differences in the anorectic activity of morphinan (e.g., naltrexone) and 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4PP) opioid receptor antagonists have been described.

Development of displacement binding and GTPgammaS scintillation proximity assays for the identification of antagonists of the micro-opioid receptor.

This article describes the development of micro-opioid receptor (MOR) binding and GTPgammaS functional SPAs as improved screening tools for the identification of MOR antagonists. Opioid receptors are members of the seven-transmembrane G protein-coupled receptor (GPCR) family and are involved in the control of various aspects of human physiology, including pain, stress, reward, addiction, respiration, gastric motility, and pituitary hormone secretion. Activation of the MOR initiates intracellular signaling pathways leading to a reduction in intracellular cyclic AMP levels, inhibition of calcium channels, and activation of potassium channels resulting in a reduction of the excitability of neurons.

Sexually transmitted diseases.

STDs are commonly encountered in emergency department patients. The emergency physician can optimize individual patient outcomes and contribute to public health STD control initiatives by: maintaining a high index of suspicion for STDs; obtaining suitable diagnostic tests and instituting appropriate empiric therapy; counseling patients regarding treatment compliance, follow-up, partner notification, and preventive measures; and 4) reporting selected STDs to public health authorities. This article provides a general review of STDs commonly encountered in the United States and gives guidelines for routine treatment of adult patients with these infections.

Determination of [35S]guanosine-5'-O-(3-thio)triphosphate binding mediated by cholinergic muscarinic receptors in membranes from Chinese hamster ovary cells and rat striatum using an anti-G protein scintillation proximity assay.

An assay for measuring agonist-stimulated [35S]guanosine-5'-O-(3-thio)triphosphate (GTPgamma35S) binding to heterotrimeric GTP binding proteins was developed for use in 96-well format using commercially available anti-G protein antibodies captured by anti-IgG-coated scintillation proximity assay beads. Use of an anti-Galphaq/11 antibody to measure GTPgamma35S binding mediated by M1, M3, and M5 receptors stably expressed in Chinese hamster ovary (CHO) cells resulted in a marked increase in agonist-stimulated/basal binding ratio compared with whole membrane binding. Pertussis toxin (PTX) treatment of CHO M1 cells before membrane preparation resulted in a marked reduction in agonist-stimulated GTPgamma35S binding to whole membranes.

Development of rapid tolerance to ethanol-stimulated serotonin release in the ventral hippocampus.

This study was designed to examine the effects of acute intraperitoneal (i.p.) ethanol injection on the extracellular levels of serotonin (5-HT) in the ventral hippocampus (vHIP) and to determine whether a single prior exposure to ethanol could alter the response to a second dose of ethanol given 24 hr later.

Effects of the antitumor agent perillyl alcohol on H-Ras vs. K-Ras farnesylation and signal transduction in pancreatic cells.

Background: Perillyl alcohol has chemotherapeutic activity against pancreas cancers that have a K-ras oncogene, and it inhibits the prenylation of Ras and other proteins in many cell types.

Materials And Methods: We tested the hypothesis that perillyl alcohol would impair Ras farnesylation and Ras signal transduction pathways in pancreatic tumor cells.

Results: In B12/13 pancreatic tumor cells that had a K-ras oncogene, perillyl alcohol inhibited total protein prenylation and decreased Ras farnesylation.

Induction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells.

Perillyl alcohol has antitumor activity toward pancreas and other cancers with low toxicity. Here, we have investigated the mechanism of action responsible for the differential sensitivity of malignant versus non-malignant pancreatic cells to the drug. We report that the rate of apoptosis is over 6-fold higher in perillyl alcohol-treated pancreatic adenocarcinoma cells than in untreated cells, and that the effect of perillyl alcohol on pancreatic tumor cells is significantly greater than its effect on non-malignant pancreatic ductal cells.

Pediatric drug therapy in the emergency department: does it meet FDA-approved prescribing guidelines?

To determine how often Food and Drug Administration (FDA)-approved age-specific prescribing guidelines were followed in pediatric emergency department (ED) patients, the charts for all children presenting to a university hospital pediatric ED during a 30-day period were reviewed. Of the 359 children who received drug therapy in the ED, 43% received one or more drugs not approved for use at the patients' respective ages. Of 296 children discharged with one or more prescriptions, 16% received a drug prescribed outside of FDA-approved guidelines based on age criteria.

Chemotherapy of pancreatic cancer with the monoterpene perillyl alcohol.

Perillyl alcohol has antitumor activity against rat mammary and liver cancer. Here, we report the chemotherapeutic effects of perillyl alcohol on pancreatic cancer. Perillyl alcohol reduced the growth of hamster pancreatic tumors to less than half that of controls (P < 0.

The use of a break-even analysis: financial analysis of a fast-track program.

Objective: To calculate the financial break-even point and illustrate how changes in third-party reimbursement and eligibility could affect a program's fiscal standing.

Methods: Demographic, clinical, and financial data were collected retrospectively for 446 patients treated in a fast-track program during June 1993. The fast-track program is located within the confines of the emergency medicine and trauma center at a 1,050-bed tertiary care Midwestern teaching hospital and provides urgent treatment to minimally ill patients.

Comparison of postoperative intraocular pressures after use of Miochol and Miostat.

Over 100 cases of standard extracapsular cataract extraction with intraocular lens implantation were reviewed and the effects of two commercially available pharmacological agents were compared. The treatment groups received either acetylcholine chloride (Miochol) or carbachol (Miostat). Intraocular pressures were measured preoperatively and 20 to 24 hours postoperatively.