Regional anesthesia decreases complications and resource utilization in shoulder arthroplasty patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142932/1/aas13063_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142932/2/aas13063.pd

Streaming potential measurements 2. Relationship between electrical and hydraulic flow patterns from rock samples during deformation

Streaming potential and resistivity measurements have been performed on Fontainebleau sandstone and Villejust quartzite samples in a triaxial device during compaction, uniaxial compression, and rupture. Measurements on individual samples do not show any clear intrinsic dependence of the streaming potential coefficient with permeability. An apparent dependence of the streaming potential coefficient with permeability is, however, observed during deformation. The effect of surface conductivity is taken into account and is small compared with the observed changes in the streaming potential coefficient. The observed dependence is therefore interpreted in terms of a difference in the evolution of the electrical and hydraulic connectivity patterns during deformation. This effect causes the streaming potential coefficient, and consequently the inferred ξ potential, to be reduced by a geometrical factor R_G representing the electrical efficiency of the hydraulic network. Estimates of the R_G factor varying between 0.2 and 0.8 for electrolyte resistivity larger than 100 Ωm are obtained by comparing the values of the ξ potential inferred from intact rock samples with the values obtained from crushed rock samples, where the geometrical effects are assumed to be negligible. The reduction of the streaming potential coefficient observed during compaction or uniaxial compression suggests that the tortuosity of the hydraulic network increases faster than the tortuosity of the electrical network. Before rupture, an increase in the streaming potential coefficient associated with the onset of dilatancy was observed for three samples of Fontainebleau sandstone and one sample of Villejust quartzite. The changes in streaming potential coefficient prior to failure range from 30% to 50%. During one experiment, an increase in the concentration of sulfate ions was also observed before failure. These experiments suggest that observable streaming potential and geochemical variations could occur before earthquakes

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Identification of the Staphylococcus aureus MSCRAMM clumping factor B (ClfB) binding site in the αC-domain of human fibrinogen

Clumping factor B (ClfB) of Staphylococcus aureus binds to cytokeratin 10 and to fibrinogen. In this study the binding site in human fibrinogen was localized to a short region within the C terminus of the Aα-chain. ClfB only bound to the Aα-chain of fibrinogen in a ligand-affinity blot and in solid-phase assays with purified recombinant fibrinogen chains. A variant of fibrinogen with wild-type Bβ- and γ-chains but with a deletion that lacked the C-terminal residues from 252–610 of the Aα-chain did not support adherence of S. aureus Newman expressing ClfB. A series of truncated mutants of the recombinant Aα-chain were tested for their ability to support adherence of S. aureus Newman ClfB+, which allowed the binding site to be localized to a short segment of the unfolded flexible repeated sequence within the C terminus of the Aα-chain. This was confirmed by two amino acid substititions within repeat 5 of the recombinant Aα-chain which did not support adherence of Newman ClfB+. Lactococcus lactis expressing ClfB mutants with amino acid substitutions (N256 and Q235) located in the putative ligand-binding trench between domains N2 and N3 of the A-domain were defective in adherence to immobilized fibrinogen and cytokeratin 10, suggesting that both ligands bind to the same or overlapping regions

Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques

ABCG2 is one of three human ATP binding cassette (ABC) transporters involved in the export from cells of a chemically and structurally diverse range of compounds. This multidrug efflux capability, together with a broad tissue distribution in the body, means that ABCG2 exerts a range of effects on normal physiology such as kidney urate transport, as well as contributing towards the pharmacokinetic profiles of many exogenous drugs. The primary sequence of ABCG2 contains only half the number of domains required for a functioning ABC transporter and so it must oligomerise in order to function, yet its oligomeric state in intact cell membranes remains uncharacterized. We have analysed ABCG2 in living cell membranes using a combination of fluorescence correlation spectroscopy, photon counting histogram analysis, and stepwise photobleaching to demonstrate a predominantly tetrameric structure for ABCG2 in the presence or absence of transport substrates. These results provide the essential basis for exploring pharmacological manipulation of oligomeric state as a strategy to modulate ABCG2 activity in future selective therapeutics

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

More than just trees: Assessing reforestation success in tropical developing countries

Rural communities in many parts of the tropics are dependent of forests for their livelihoods and for environmental services. Forest resources in the tropics have declined rapidly over the past century and therefore many developing countries in the tropics have reforestation programs. Although reforestation is a long-term process with long-term benefits, existing evaluations of the success of these programs tends to focus on short-term establishment success indicators. This paper presents a review of reforestation assessment that highlights the need to not only consider short-term establishment success, but also longer-term growth and maturation success, environmental success and socio-economic success. In addition, we argue that reforestation assessment should not be based on success indicators alone, but should incorporate the drivers of success, which encompasses an array of biophysical, socio-economic, institutional and project characteristics. This is needed in order to understand the reasons why reforestation projects succeed or fail and therefore to design more successful projects in future. The paper presents a conceptual model for reforestation success assessment that links key groups of success indicators and drivers. This conceptual model provides the basis for a more comprehensive evaluation of reforestation success and the basis for the development of predictive systems-based assessment models. These models will be needed to better guide reforestation project planning and policy design and therefore assist rural communities in tropical developing countries to alleviate poverty and achieve a better quality of life

5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

oai:ojs.pkp.sfu.ca:article/31555-HT receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-HT receptors [194] and subsequently revised [176]) are, with the exception of the ionotropic 5-HT3 class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing that produces isoforms of the 5-HT2A (non-functional), 5-HT2C (non-functional), 5-HT4, 5-HT6 (non-functional) and 5-HT7 receptors. Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482]. Most 5-HT receptors (except 5-ht1e and 5-ht5b) play specific roles mediating functional responses in different tissues (reviewed by [463, 382])