Several peptide fragments are produced by proteolytic cleavage of the opioid peptide precursor proenkephalin A, and among these are a number of enkephalin fragments, in particular bovine adrenal ...medulla peptide 22 (BAM22). These peptide products have been implicated in diverse biological functions, including analgesia. We have cloned a newly identified family of 'orphan' G protein--coupled receptors (GPCRs) and demonstrate that BAM22 and a number of its fragments bind to and activate these receptors with nanomolar affinities. This family of GPCRs is uniquely localized in the human and rat small sensory neuron, and we called this family the sensory neuron--specific G protein--coupled receptors (SNSRs). Receptors of the SNSR family are distinct from the traditional opioid receptors in their insensitivity to the classical opioid antagonist naloxone and poor activation by opioid ligands. The unique localization of SNSRs and their activation by proenkephalin A peptide fragments indicate a possible function for SNSRs in sensory neuron regulation and in the modulation of nociception.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract The addition of large amounts of antibiotics to bone cement provides a convenient local delivery, but may influence the compressive properties of the cement. Flucloxacillin and vancomycin ...were added to Simplex P (Stryker, Limerick, Ireland) and VersaBond (Smith & Nephew) cements. Tripling the antibiotic dose from 2 to 6 g had little effect on the static compressive properties 24 hours after curing. After 4 weeks in phosphate-buffered saline, there was marked decrease in properties with the addition of antibiotics. Compressive strength of cements with 6 g of antibiotic was reduced to near or below the ASTM and ISO minimum of 70 MPa after 4 weeks in phosphate-buffered saline. Microcomputer tomography revealed increased porosity and clumping of the radiopacifier with the addition of antibiotics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We compared the biogeochemical cycling of phosphorus (P) in northern hardwood forest plots invaded by exotic earthworms versus adjacent uninvaded reference plots. In three of the six pairs of plots, ...earthworm invasion resulted in significantly more total P in the upper 12 cm of soil. The finding of increased amounts of unavailable and occluded inorganic P forms in the invaded plots suggests that earthworm activity mobilized unweathered soil particles from deeper layers of the soil, increasing the stocks of total P in surface soils. In two pairs of plots, the earthworm-invaded soils had less total P than the reference soils. In these plots, earthworm activity resulted in augmented rates of P cycling and alteration of the physical structure of the soil that increased loss of P in leaching water, reducing the total amount of P. We hypothesize that the different effects of earthworm invasion on the soil P cycle result from unique characteristics of the ecological groups of earthworms dominating each site. The invaded plots with increased total P were dominated by the anecic species Lumbricus terrestris, a large earthworm that constructs deep, vertical burrows and is effective at moving soil materials from and to deeper layers of the profile. In contrast, the earthworm-invaded plots where the total P in the surface soil decreased were dominated by the epiendogeic species L. rubellus, which feeds and lives in the upper organic layers of the soil. In these plots, earthworms significantly increased the amount of readily exchangeable P in the soil, increasing the loss of this element in leaching water.
We have analyzed several cases of Beckwith-Wiedemann syndrome (BWS) with Wilms' tumor in a familial setting, which give insight into the complex controls of imprinting and gene expression in the ...chromosome 11p15 region. We describe a 2.2-kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting center eliminating three target sites of the chromatin insulator protein CTCF that we believe here is necessary, but not sufficient, to cause BWS and Wilms' tumor. Maternal inheritance of the deletion is associated with IGF2 loss of imprinting and up-regulation of IGF2 mRNA. However, in at least one affected family member a second genetic lesion (a duplication of maternal 11p15) was identified and accompanied by a further increase in IGF2 mRNA levels 35-fold higher than control values. Our results suggest that the combined effects of the H19/IGF2-imprinting center microdeletion and 11p15 chromosome duplication were necessary for manifestation of BWS.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Many practitioners are not familiar with many alternative medicine techniques. ...the reader should view this CECD as the best attempt of the ACCF to inform and guide clinical practice in an area ...where rigorous evidence is not yet available or the evidence to date is not widely accepted. Herbal Preparation Suggested Laboratory Analysis Antidote Cardiac toxins   Ch'an Su Serum digoxin, potassium Digoxin Fab Foxglove Serum digoxin, potassium Digoxin Fab Oleander Serum digoxin, potassium Digoxin Fab Squill Serum digoxin, potassium Digoxin Fab Central nervous system toxins   Henbane None Physostigmine Jimsonweed (Datura) None Physostigmine Mandrake None Physostigmine Gastrointestinal toxins   Aloe Serum electrolytes Potassium repletion Buckthorn Serum electrolytes Potassium repletion Cascara Serum electrolytes Potassium repletion Fo-Ti Serum electrolytes Potassium repletion Senna Serum electrolytes Potassium repletion Heavy metals Ag, As, Au, Cd, Cr, Cu, Hg, Pb, Th, or Zn Abdominal radiograph Metal chelator Hematologic toxins   Dong Quai INR Vitamin K1 Tonka bean INR Vitamin K1 Woodruff INR Vitamin K1 Hepatotoxins   Pennyroyal oil AST/ALT N-acetylcysteine Pyrrolizidine alkaloids AST/ALT None available Salicylates   Medicated oils, etc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A high-throughput screening campaign to discover small molecule leads for the treatment of bone disorders concluded with the discovery of a compound with a 2-aminopyrimidine template that targeted ...the Wnt β-catenin cellular messaging system. Hit-to-lead in vitro optimization for target activity and molecular properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent pharmacokinetic properties and showed a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration.
Cervical spine range of motion (ROM) assessment has long been carried out via use of the universal goniometer (UG) as an objective tool in the evaluation of patient rehabilitation pre- and ...post-operatively. The advent of novel ROM assessment technology, such as HALO digital goniometer (DG), presents an avenue for research and potential application within clinical and surgical settings. The objective of this study was to examine the reliability and validity of the HALO DG in the assessment of the active ROM of the cervical spine.
One hundred healthy subjects were recruited for the study and were split into two groups to be assessed by either physiotherapists or medical students. The methodology for cervical spine ROM assessment was carried out per the American Association of Orthopaedic Surgeons (AAOS) guidelines. The reliability analysis was completed using IBM SPSS Statistics 25, calculating the intraclass correlation coefficients (ICC) to determine both the intra- and inter-rater reliability of the device.
Inter-rater reliability within the physiotherapist cohort with the DG (ICCr =0.477, 0.718, 0.551) was higher compared to the UG (ICCr =0.380, 0.510, 0.255) for active cervical flexion, lateral flexion, and rotation, respectively. The UG (ICCr =0.819) showed better reliability versus the DG (ICCr =0.780) when assessing cervical extension. Similarly, in the medical student cohort, the DG outperformed the UG in all movement except cervical lateral flexion. When assessing for intra-rater reliability, the DG (ICCm =0.507, 0.773, 0.728, 0.691) performed better than the UG (ICCm =0.487, 0.529, 0.532, 0.585) in cervical flexion, extension, lateral flexion, and rotation, respectively.
The present validation study identified the DG as a reliable substitute for the UG.
Midcarpal arthrodesis is a treatment of choice in patients with midcarpal arthritis. Traditionally a four corner fusion has been favoured, however recent research has shown improved results when the ...triquetrum and scaphoid are excised. There is no clear evidence as to which remaining bones should be fused or which implants should be used. The purpose of this study is to compare the biomechanics of midcarpal arthrodesis after scaphoid and triquetrum excision, using memory staples or cannulated screws, in recognised construct patterns.
36 identical sets of carpal bones were 3D printed from acetyl butyl styrene. Midcarpal arthrodeses were performed in three configurations with shape memory alloy staples or headless compression screws. This gave 6 treatment groups; lunocapitate single staple or screw, lunocapitate with 2 staples or screws, three corner fusion with 2 staples or screws. Peak torque to distraction was measured and analysed.
The peak torque to distraction was significantly greater in almost all constructs utilizing screws compared to staples, with two lunocapitate screws having the highest peak torque at both 1 and 3 mm distraction with 244 Nmm and 749 Nmm respectively (p < 0.05).
Constructs utilizing screws have a peak torque to distraction significantly higher when compared to staples. Our recommendation when performing a midcarpal arthrodesis after scaphoid and trapezium excision is to fuse the midcarpal joint with 2 headless compression screws.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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