Detection of urological cancers by the signature of organic volatile compounds in urine, from dogs to electronic noses.

Purpose Of Review: Urine volatile organic compound (VOC) testing for early detection of urological cancers is a minimally invasive and promising method. The objective of this review was to present the results of recently published work on this subject.

Recent Findings: Organic volatile compounds are produced through oxidative stress and peroxidation of cell membranes, and they are eliminated through feces, urine, and sweat.

Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling.

Increasing evidence supports a relationship between lipid metabolism and mental health. In particular, the biostatus of polyunsaturated fatty acids (PUFAs) correlates with some symptoms of psychiatric disorders, as well as the efficacy of pharmacological treatments. Recent findings highlight a direct association between brain PUFA levels and dopamine transmission, a major neuromodulatory system implicated in the etiology of psychiatric symptoms.

Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane.

The γ-aminobutyric acid type B (GABA) receptor is a prototypical family C G protein-coupled receptor (GPCR) that plays a key role in the regulation of synaptic transmission. Although growing evidence suggests that GPCR signaling in neurons might be highly organized in time and space, limited information is available about the mechanisms controlling the nanoscale organization of GABA receptors and other GPCRs on the neuronal plasma membrane. Using a combination of biochemical assays in vitro, single-particle tracking, and super-resolution microscopy, we provide evidence that the spatial organization and diffusion of GABA receptors on the plasma membrane are governed by dynamic interactions with filamin A, which tethers the receptors to sub-cortical actin filaments.

Cost-Effectiveness Analysis of Evolocumab in Adult Patients with Atherosclerotic Cardiovascular Disease in Canada.

Introduction: To evaluate the cost-effectiveness of evolocumab when added to standard of care lipid-lowering treatment (LLT) for patients with atherosclerotic cardiovascular disease (ASCVD) who cannot adequately control their low-density lipoprotein cholesterol (LDL-C) despite optimized LLT in Canada.

Methods: An incremental cost-utility analysis was conducted using a Markov cohort state transition model adapted to the Canadian setting. Analyses were conducted from a public health and societal perspective using a lifetime time horizon for Canada.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women at very high risk of fracture in Canada.

Unlabelled: This study evaluated the cost-effectiveness of 1 year of romosozumab followed by alendronate versus oral bisphosphonates alone in women with postmenopausal osteoporosis at very high risk for fracture in Canada. Results showed that romosozumab sequenced to alendronate is a cost-effective treatment option, dominating both alendronate and risedronate alone.

Purpose: To demonstrate the value of romosozumab sequenced to alendronate compared to alendronate or risedronate alone, for the treatment of osteoporosis in postmenopausal women with a history of osteoporotic fracture and who are at very high risk for future fracture in Canada.

Heterotrimeric G Protein Subunit Gαq Is a Master Switch for Gβγ-Mediated Calcium Mobilization by Gi-Coupled GPCRs.

Mechanisms that control mobilization of cytosolic calcium [Ca] are key for regulation of numerous eukaryotic cell functions. One such paradigmatic mechanism involves activation of phospholipase Cβ (PLCβ) enzymes by G protein βγ subunits from activated Gα-Gβγ heterotrimers. Here, we report identification of a master switch to enable this control for PLCβ enzymes in living cells.

Super-resolution imaging reveals the nanoscale organization of metabotropic glutamate receptors at presynaptic active zones.

G protein-coupled receptors (GPCRs) play a fundamental role in the modulation of synaptic transmission. A pivotal example is provided by the metabotropic glutamate receptor type 4 (mGluR4), which inhibits glutamate release at presynaptic active zones (AZs). However, how GPCRs are organized within AZs to regulate neurotransmission remains largely unknown.

Support for the Deployment of Climate Engineering: A Comparison of Ten Different Technologies.

Due to the renewed increase in CO emissions seen in recent years, the deployment of climate engineering technologies might become necessary if the global temperature increase is to be kept within 1.5 °C. If climate engineering is to be deployed, however, public support is required.

Selective and Wash-Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single-Molecule Imaging of μ-Opioid Receptor Dimerization.

μ-Opioid receptors (μ-ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ-ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ-OR antagonist E-p-nitrocinnamoylamino-dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity.

Biophysical Insight on the Membrane Insertion of an Arginine-Rich Cell-Penetrating Peptide.

Cell-penetrating peptides (CPPs) are short peptides that can translocate and transport cargoes into the intracellular milieu by crossing biological membranes. The mode of interaction and internalization of cell-penetrating peptides has long been controversial. While their interaction with anionic membranes is quite well understood, the insertion and behavior of CPPs in zwitterionic membranes, a major lipid component of eukaryotic cell membranes, is poorly studied.

The Contribution of Differential Scanning Calorimetry for the Study of Peptide/Lipid Interactions.

Membrane-active peptides include a variety of molecules such as antimicrobial (AMP), cell-penetrating (CPP), viral, and amyloid peptides that are implicated in several pathologies. They constitute important targets because they are either at the basis of novel therapies (drug delivery for CPPs or antimicrobial activity for AMPs) or they are the agents causing these pathologies (viral and amyloid peptides). They all share the common property of interacting with the cellular lipid membrane in their mode of action.

Hot spots for GPCR signaling: lessons from single-molecule microscopy.

G protein-coupled receptors (GPCRs) are among the best-studied membrane receptors, mainly due to their central role in human physiology, involvement in disease and relevance as drug targets. Although biochemical and pharmacological studies have characterized the main steps in GPCR signaling, how GPCRs produce highly specific responses in our cells remains insufficiently understood. New developments in single-molecule microscopy have made it possible to study the protein-protein interactions at the basis of GPCR signaling in previously inconceivable detail.

An international study of the quality of life of adult patients treated with home parenteral nutrition.

Background & Aims: Home parenteral nutrition-quality of life (HPN-QOL) is a self-assessment tool for the measurement of QOL in patients on HPN. The aims of this study were: to re-assess the basic psychometric properties of the HPN-QOL in a multinational sample of adult patients; to provide a description of QOL dimensions by short and long HPN treatment duration; to explore clinical factors potentially associated to QOL scores.

Methods: Patients (n = 699) from 14 countries completed the HPN-QOL.

Medical commitment to Lean: an inductive model development.

Purpose The purpose of this paper is to study the factors influencing doctors' involvement in Lean change initiatives in public healthcare organizations in Canada. Design/methodology/approach An inductive research was conducted over a three-year span studying Lean implementation across three healthcare organizations in Canada. Various interviews were conducted with healthcare actors.

Single-Molecule Microscopy Reveals Dynamic FLNA Interactions Governing SSTR2 Clustering and Internalization.

The cytoskeletal protein filamin A (FLNA) has been suggested to play an important role in the responsiveness of GH-secreting pituitary tumors to somatostatin receptor subtype 2 (SSTR2) agonists by regulating SSTR2 expression and signaling. However, the underlying mechanisms are unknown. In this study, we use fast multicolor single-molecule microscopy to image individual SSTR2 and FLNA molecules at the surface of living cells with unprecedented spatiotemporal resolution.

IMPUTOR: Phylogenetically Aware Software for Imputation of Errors in Next-Generation Sequencing.

We introduce IMPUTOR, software for phylogenetically aware imputation of missing haploid nonrecombining genomic data. Targeted for next-generation sequencing data, IMPUTOR uses the principle of parsimony to impute data marked as missing due to low coverage. Along with efficiently imputing missing variant genotypes, IMPUTOR is capable of reliably and accurately correcting many nonmissing sites that represent spurious sequencing errors.

Interspecific differences in biochemical and behavioral biomarkers in endogeic earthworms exposed to ethyl-parathion.

Earthworms are common organisms in the soil toxicity-testing framework, and the epigeic Eisenia andrei and E. fetida are the recommended species. However, Eisenia species are rarely found in agricultural soils and recent studies have pointed out endogeic species are more sensitive to pesticides than Eisenia.

Altered muscarinic receptor expression in the cerebral cortex of epileptic rats: restorative role of Withania somnifera.

Temporal lobe epilepsy involves a sequence of events that can lead to neurotransmitter signalling alterations. There are many herbal extracts considered to be alternative therapeutic methods to manage epilepsy. In this study, we investigated the effect of Withania somnifera (WS) root extract and withanolide A (WA) in the management of temporal lobe epilepsy.

Tap versus bottled water consumption: The influence of social norms, affect and image on consumer choice.

What drives consumers to choose bottled water instead of tap water where the latter is safe, accessible, costs far less, and in spite of its environmental impacts? This research investigates the influence of hitherto unexplored psychological drivers in an attempt to generate a more holistic understanding of the phenomenon, and strategies for designing more effective consumption reduction campaigns. Using data from an internet survey of Swiss and German respondents (N = 849) we investigated the role of, social norms, affect and image on water consumption. Results suggest that these psychological factors play a role in water consumption choice.

Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots.

G-protein-coupled receptors mediate the biological effects of many hormones and neurotransmitters and are important pharmacological targets. They transmit their signals to the cell interior by interacting with G proteins. However, it is unclear how receptors and G proteins meet, interact and couple.

Adaptation in : From Stress to Disease.

is a food-borne pathogen that causes diarrheal disease in humans. After ingestion, experiences in the human gastro-intestinal tract abiotic physical variables encountered in food, such as acidic pH in the stomach and changing oxygen conditions in the human intestine. responds to environmental changing conditions (stress) by reversibly adjusting its physiology to maximize resource utilization while maintaining structural and genetic integrity by repairing and minimizing damage to cellular infrastructure.

Geometry of Chemical Beam Vapor Deposition System for Efficient Combinatorial Investigations of Thin Oxide Films: Deposited Film Properties versus Precursor Flow Simulations.

An innovative deposition system has been developed to construct complex material thin films from single-element precursors by chemical beam vapor deposition (CBVD). It relies on well distributed punctual sources that emit individually controlled precursor beams toward the substrate under high vacuum conditions combined with well designed cryo-panel surfaces that avoid secondary precursor sources. In this configuration the impinging flows of all precursors can be calculated at any substrate point considering the controlled angular distribution of the emitted beams and the ballistic trajectory of the molecules.