Oleic acid released by sensory neurons inhibits TRPV1-mediated thermal hypersensitivity via GPR40.

Noxious stimuli activate nociceptive sensory neurons, causing action potential firing and the release of diverse signaling molecules. Several peptides have already been identified to be released by sensory neurons and shown to modulate inflammatory responses and inflammatory pain. However, it is still unclear whether lipid mediators can be released upon sensory neuron activation to modulate intercellular communication.

Reductive Elimination From Tetra-Alkyl Cuprates [MeCu(CF)] (n=0-4): Beyond Simple Oxidation States.

In recent years, the electronic structures of organocuprates in general and the complex [Cu(CF)] in particular have attracted significant interest. A possible key indicator in this context is the reactivity of these species. Nonetheless, this aspect has received only limited attention.

Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction.

Introduction: P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found.

Opposing effects of the purinergic P2X7 receptor on seizures in neurons and microglia in male mice.

Background: The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood.

Phase transition of GvpU regulates gas vesicle clustering in bacteria.

Gas vesicles (GVs) are microbial protein organelles that support cellular buoyancy. GV engineering has multiple applications, including reporter gene imaging, acoustic control and payload delivery. GVs often cluster into a honeycomb pattern to minimize occupancy of the cytosol.

Unimolecular Reactivity of [Cu(R)(CF ) ] Complexes (R=Organyl): Stepwise versus Concerted Mechanism in Copper-Mediated Trifluoromethylation.

The cuprate complexes [Cu(R)(CF ) ] (R=organyl) offer an efficient synthetic access to valuable trifluoromethylation products RCF . Here, electrospray-ionization mass spectrometry is used to analyze the formation of these intermediates in solution and probe their fragmentation pathways in the gas phase. Furthermore, the potential energy surfaces of these systems are explored by quantum chemical calculations.

Contemporary Considerations for Establishing Reference Methods for Antibacterial Susceptibility Testing.

Antibacterial susceptibility testing (AST) is performed to guide therapy, perform resistance surveillance studies, and support development of new antibacterial agents. For 5 decades, broth microdilution (BMD) has served as the reference method to assess activity of antibacterial agents against which both novel agents and diagnostic tests have been measured. BMD relies on in vitro inhibition or killing of bacteria.

Macrophages and glia are the dominant P2X7-expressing cell types in the gut nervous system-No evidence for the role of neuronal P2X7 receptors in colitis.

The blockade or deletion of the pro-inflammatory P2X7 receptor channel has been shown to reduce tissue damage and symptoms in models of inflammatory bowel disease, and P2X7 receptors on enteric neurons were suggested to mediate neuronal death and associated motility changes. Here, we used P2X7-specific antibodies and nanobodies, as well as a bacterial artificial chromosome transgenic P2X7-EGFP reporter mouse model and P2rx7 controls to perform a detailed analysis of cell type-specific P2X7 expression and possible overexpression effects in the enteric nervous system of the distal colon. In contrast to previous studies, we did not detect P2X7 in neurons but found dominant expression in glia and macrophages, which closely interact with the neurons.

Prevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible Staphylococcus aureus Isolates.

Antistaphylococcal penicillins and cefazolin remain the primary treatments for infections with methicillin-susceptible Staphylococcus aureus (MSSA). The cefazolin inoculum effect (CzIE) causes the cefazolin MIC to be elevated in proportion to the number of bacteria in the inoculum. The objective of this multicenter study was to evaluate the prevalence of the CzIE in North American MSSA isolates.

An exploratory investigation of predictors of outcome in face-to-face and online cognitive-behavioural therapy for bulimia nervosa.

Objective: Cognitive-behavioural therapy (CBT) delivered face-to-face and via the internet reduces bulimia nervosa (BN) symptoms. However, our empirical understanding of factors affecting patient outcomes is limited.

Method: Using data from a randomised, controlled trial comparing internet-based (CBT4BN, n = 78) with face-to-face (CBTF2F, n = 71) group CBT (97% female, M = 28 years), we examined general treatment (across conditions) and modality-specific predictors of end-treatment and 1-year outcomes (abstinence, binge-eating frequency, purging frequency).

Mechanisms of coordinating hyaluronan and glycosaminoglycan production by nucleotide sugars.

Hyaluronan is a versatile macromolecule capable of an exceptional range of functions from cushioning and hydration to dynamic signaling in development and disease. Because of its critical roles, hyaluronan production is regulated at multiple levels including epigenetic, transcriptional, and posttranslational control of the three hyaluronan synthase (HAS) enzymes. Precursor availability can dictate the rate and amount of hyaluronan synthesized and shed by the cells producing it.

Oxidized linoleic acid metabolites maintain mechanical and thermal hypersensitivity during sub-chronic inflammatory pain.

Inflammatory pain serves as a protective defense mechanism which becomes pathological when it turns into chronic inflammatory pain. This transition is mediated by a variety of peripheral mediators that sensitize nociceptors and increase pain perception in sensory neurons. Besides cytokines, chemokines and growth factors, accumulating evidence shows that oxidized lipids, such as eicosanoids and oxidized linoleic acid metabolites, contribute to this sensitization process.

Increased expression of the ATP-gated P2X7 receptor reduces responsiveness to anti-convulsants during status epilepticus in mice.

Background And Purpose: Refractory status epilepticus is a clinical emergency associated with high mortality and morbidity. Increasing evidence suggests neuroinflammation contributes to the development of drug-refractoriness during status epilepticus. Here, we have determined the contribution of the ATP-gated P2X7 receptor, previously linked to inflammation and increased hyperexcitability, to drug-refractory status epilepticus and its therapeutic potential.

Impact of CYP2B6 genotype, tuberculosis therapy, and formulation on efavirenz pharmacokinetics in infants and children under 40 months of age.

Objective: Dosing efavirenz (EFV) in children less than 3 years of age is challenging due to large variability in drug levels. This study evaluated differences in pharmacokinetics with tuberculosis (TB) therapy, formulation, age, and CYP2B6 genotype.

Design: Pharmacokinetic data from three IMPAACT/PACTG studies (P382, P1021, and P1070) for children initiating therapy less than 40 months of age were evaluated.

Footprint evidence of early hominin locomotor diversity at Laetoli, Tanzania.

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity.

Altered glucuronidation deregulates androgen dependent response profiles and signifies castration resistance in prostate cancer.

Glucuronidation controls androgen levels in the prostate and the dysregulation of enzymes in this pathway is associated with castration resistant prostate cancer. UDP-glucose dehydrogenase (UGDH) produces UDP-glucuronate, the essential precursor for glucuronidation, and its expression is elevated in prostate cancer. We compared protein and metabolite levels relevant to the glucuronidation pathway in five prostate cancer patient-derived xenograft models paired with their isogenic counterparts that were selected for castration resistant (CR) recurrence.

Implications of pretreatment incisor inclinations for the achievement of cephalometric normal values-a study on two patient collectives.

Purpose: The objective was to clarify whether standardized multibracket therapies-differing only in finishing-wire dimensions (0.016 × 0.022 inch vs.

A new short-faced archosauriform from the Upper Triassic Placerias/Downs' quarry complex, Arizona, USA, expands the morphological diversity of the Triassic archosauriform radiation.

The Placerias/Downs' Quarry complex in eastern Arizona, USA, is the most diverse Upper Triassic vertebrate locality known. We report a new short-faced archosauriform, Syntomiprosopus sucherorum gen. et sp.

Safety, immunogenicity, and transplacental antibody transport of conjugated and polysaccharide pneumococcal vaccines administered to pregnant women with HIV: a multicentre randomised controlled trial.

Background: Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy.

Methods: This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil.

Validation of the PhageDx™ Listeria Assay for Detection of Listeria Spp. on Stainless Steel and Ceramic Environmental Surfaces AOAC Performance Tested MethodSM 102005.

Background: The PhageDx™ Listeria Assay is a simple, specific, and sensitive assay based on the infection of Listeria spp. by selected bacteriophages and the resultant expression of a luciferase reporter gene. Results are generated in as little as 24.

Pharmacokinetics and safety of early nevirapine-based antiretroviral therapy for neonates at high risk for perinatal HIV infection: a phase 1/2 proof of concept study.

Background: With increasing intention to treat HIV as early as possible, evidence to confirm the safety and therapeutic drug concentrations of a nevirapine-based antiretroviral regimen in the early neonatal period is needed. This study aims to establish dosing of nevirapine for very early treatment of HIV-exposed neonates at high risk of HIV acquisition.

Methods: IMPAACT P1115 is a multinational phase 1/2 proof-of-concept study in which presumptive treatment for in-utero HIV infection is initiated within 48 h of birth in HIV-exposed neonates at high risk of HIV acquisition.

Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus.

Background: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined.

Methods: Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery.

Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping.

The World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women.