The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C

Opioids are some of the most efficacious analgesics used in humans. Prolonged administration of opioids, however, often causes the development of drug tolerance, thus limiting their effectiveness. To explore the molecular basis of those mechanisms that may contribute to opioid tolerance, we have isolated a cDNA for the human mu opioid receptor, the target of such opioid narcotics as morphine, codeine, methadone, and fentanyl. The receptor encoded by this cDNA is 400 amino acids long with 94% sequence similarity to the rat mu opioid receptor. Transient expression of this cDNA in COS-7 cells produced high-affinity binding sites to mu-selective agonists and antagonists. This receptor displays functional coupling to a recently cloned G-protein-activated K+ channel. When both proteins were expressed in Xenopus oocytes, functional desensitization developed upon repeated stimulation of the mu opioid receptor, as observed by a reduction in K+ current induced by the second mu receptor activation relative to that induced by the first. The extent of desensitization was potentiated by both the multifunctional calcium/calmodulin-dependent protein kinase and protein kinase C. These results demonstrate that kinase modulation is a molecular mechanism by which the desensitization of mu receptor signaling may be regulated at the cellular level, suggesting that this cellular mechanism may contribute to opioid tolerance in humans

Relativistic wave equations for interacting massive particles with arbitrary half-intreger spins

New formulation of relativistic wave equations (RWE) for massive particles with arbitrary half-integer spins s interacting with external electromagnetic fields are proposed. They are based on wave functions which are irreducible tensors of rank $n ($n=s-\frac12$) antisymmetric w.r.t. n pairs of indices, whose components are bispinors. The form of RWE is straightforward and free of inconsistencies associated with the other approaches to equations describing interacting higher spin particles

International consensus on the most useful physical examination tests used by physiotherapists for patients with headache: A Delphi study

Background: A wide range of physical tests have been published for use in the assessment of musculoskeletal dysfunction in patients with headache. Which tests are used depends on a physiotherapist's clinical and scientific background as there is little guidance on the most clinically useful tests. Objectives: To identify which physical examination tests international experts in physiotherapy consider the most clinically useful for the assessment of patients with headache. Design/methods: Delphi survey with pre-specified procedures based on a systematic search of the literature for physical examination tests proposed for the assessment of musculoskeletal dysfunction in patients with headache. Results: Seventeen experts completed all three rounds of the survey. Fifteen tests were included in round one with eleven additional tests suggested by the experts. Finally eleven physical examination tests were considered clinically useful: manual joint palpation, the cranio-cervical flexion test, the cervical flexion-rotation test, active range of cervical movement, head forward position, trigger point palpation, muscle tests of the shoulder girdle, passive physiological intervertebral movements, reproduction and resolution of headache symptoms, screening of the thoracic spine, and combined movement tests. Conclusions: Eleven tests are suggested as a minimum standard for the physical examination of musculoskeletal dysfunctions in patients with headache

Fungal Planet description sheets: 1436–1477

Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilax glyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo