Evidence of reliability and responsiveness for the hip outcome score.

Purpose: The purpose of this study was to offer evidence of test-retest reliability and responsiveness of both the Hip Outcome Score (HOS) activities of daily living (ADL) and sports subscales.

Methods: We included 126 subjects in this study. They had a mean age of 41 years (range, 13 to 80 years; SD, 16).

Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties.

Among the diverse sets of nicotinic acetylcholine receptors (nAChRs), the alpha7 subtype is highly expressed in the hippocampus and cortex and is thought to play important roles in a variety of cognitive processes. In this review, we describe the properties of a novel biaryl diamine alpha7 nAChR agonist, A-582941. A-582941 was found to exhibit high-affinity binding and partial agonism at alpha7 nAChRs, with acceptable pharmacokinetic properties and excellent distribution to the central nervous system (CNS).

Covalency trends in group IV metallocene dichlorides. chlorine K-edge X-ray absorption spectroscopy and time dependent-density functional theory.

For 3-5d transition-metal ions, the (C5R5)2MCl2 (R = H, Me for M = Ti, Zr, Hf) bent metallocenes represent a series of compounds that have been central in the development of organometallic chemistry and homogeneous catalysis. Here, we evaluate how changes in the principal quantum number for the group IV (C5H5)2MCl2 (M = Ti, Zr, Hf; 1- 3, respectively) complexes affects the covalency of M-Cl bonds through application of Cl K-edge X-ray Absorption Spectroscopy (XAS). Spectra were recorded on solid samples dispersed as a thin film and encapsulated in polystyrene matrices to reliably minimize problems associated with X-ray self-absorption.

Heel pain--plantar fasciitis: clinical practice guildelines linked to the international classification of function, disability, and health from the orthopaedic section of the American Physical Therapy Association.

The Heel Pain-Plantar Fasciitis Guidelines link the International Classification of Functioning, Disability, and Health (ICF) body structures (Ligaments and fascia of ankle and foot, and Neural structures of lower leg) and the ICF body functions (Pain in lower limb, and Radiating pain in a segment or region) with the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD) health condition (Plantar fascia fibromatosis/Plantar fasciitis). The purpose of these practice guidelines is to describe evidence-based orthopaedic physical therapy clinical practice and provide recommendations for (1) examination and diagnostic classification based on body functions and body structures, activity limitations, and participation restrictions, (2) prognosis, (3) interventions provided by physical therapists, and (4) assessment of outcome for common musculoskeletal disorders.

Validity of the Foot and Ankle Ability Measure in athletes with chronic ankle instability.

Context: The Foot and Ankle Ability Measure (FAAM) is a region-specific, non-disease-specific outcome instrument that possesses many of the clinimetric qualities recommended for an outcome instrument. Evidence of validity to support the use of the FAAM is available in individuals with a wide array of ankle and foot disorders. However, additional evidence to support the use of the FAAM for those with chronic ankle instability (CAI) is needed.

Crown ether inclusion complexes of the early actinide elements, [AnO2(18-crown-6)]n+, An = U, Np, Pu and n = 1, 2: a relativistic density functional study.

The title compounds, [AnO2(18-crown-6)]n+, An = U, Np, and Pu and n = 1 and 2, as well as the related (experimentally observed) complex [UO2(dicyclohexyl-18-crown-6)]2+ are studied using relativistic density functional theory (DFT). Different relativistic methods (large-core and small-core effective core potentials, all-electron scalar four-component) and two flavors of approximate DFT (B3LYP and PBE) are used. Calculated bond lengths agree well with the available experimental data for the NpV complex, while larger differences for the UVI complexes appear to be related to the large uncertainties in the experimental data.

The role of spatial location in auditory search.

The majority of research findings to date indicate that spatial cues play a minor role in enhancing listeners' ability to parse and detect a sound of interest when it is presented in a complex auditory scene comprising multiple simultaneous sounds. Frequency and temporal differences between sound streams provide more reliable cues for scene analysis as well as for directing attention to relevant auditory 'objects' in complex displays. The present study used naturalistic sounds with varying spectro-temporal profiles to examine whether spatial separation of sound sources can enhance target detection in an auditory search paradigm.

Spectral integration time of the auditory localisation system.

For the elevation and front-versus-back hemifield of a sound source to be accurately determined, the sound must contain a broad range of frequencies. Experiment 1 of this study examined the spectral integration time of the auditory localisation system by measuring the accuracy with which frequency-modulated (FM) tones of modulation periods ranging from 0.5 to 200 ms can be localised.

Sound localisation during illusory self-rotation.

Auditory elevation localisation was investigated under conditions of illusory self-rotation (i.e., vection) induced by movement of wide-field visual stimuli around participants' z-axes.

Spatial audio displays improve the detection of target messages in a continuous monitoring task.

Objective: The detection of target messages in a background of competing speech and the identification of the color/number combinations in those messages were examined in a continuous monitoring task.

Background: Previous research has shown that if listeners know when and where to listen, speech-on-speech intelligibility is improved when signals are presented via a 3-D audio display as compared with a diotic display. However, the effect of display type on detection of infrequent target messages in a continuous monitoring task has not been examined.

Systematic studies of early actinide complexes: uranium(IV) fluoroketimides.

The reaction of (C5Me5)2U(CH3)2 with 2 equiv of N[triple bond]C-ArF gives the fluorinated uranium(IV) bis(ketimide) complexes (C5Me5)2U[-N=C(CH3)(ArF)]2 [where ArF=2-F-C6H4 (4), 3-F-C6H4 (5), 4-F-C6H4 (6), 2,6-F2-C6H3 (7), 3,5-F2-C6H3 (8), 2,4,6-F3-C6H2 (9), 3,4,5-F3-C6H2 (10), and C6F5 (11)]. These have been characterized by single-crystal X-ray diffraction, 1H and 19F NMR, cyclic voltammetry, UV-visible-near-IR absorption spectroscopy, and variable-temperature magnetic susceptibility. Density functional theory (DFT) results are reported for complexes 6 and 11 for comparison with experimental data.

Evidence of validity for the hip outcome score in hip arthroscopy.

Purpose: The purpose of this study was to provide evidence of validity for the Hip Outcome Score (HOS) as an outcome instrument in hip arthroscopy.

Methods: We mailed the short form 36 (SF-36) and HOS questionnaires, as well as questionnaires regarding self-reported current activity level (normal, nearly normal, abnormal, or severely abnormal) and self-reported surgical outcome (excellent/good or fair/poor), to 337 subjects. Medical records were used to collect surgical and demographic information.

Functional consequences of methionine oxidation of hERG potassium channels.

Reactive species oxidatively modify numerous proteins including ion channels. Oxidative sensitivity of ion channels is often conferred by amino acids containing sulfur atoms, such as cysteine and methionine. Functional consequences of oxidative modification of methionine in human ether à go-go related gene 1 (hERG1), which encodes cardiac I(Kr) channels, are unknown.

Posttraumatic ankle arthritis: an update on conservative and surgical management.

This manuscript offers current information regarding the examination, conservative treatment, and surgical treatment for individuals with posttraumatic arthritis. Although inflammatory and osteoarthritis can occur, posttraumatic arthritis is the most common form of arthritis to affect the ankle. Posttraumatic ankle arthritis occurs in a generally younger, active population.

Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension.

Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency.

Hydroxypropyl beta-cyclodextrins: a misleading vehicle for the in vitro hERG current assay.

Delayed cardiac repolarization and fatal proarrhythmia have been linked to block of the repolarizing current, Ikr or hERG (human ether-a-go-go related gene) current. Thus, determining the potency of hERG block is critical in evaluating cardiac safety during preclinical development. Hydroxypropyl beta-cyclodextrins (HbetaC) are cyclic oligosaccharides used to enhance drug solubility.

Control of electronic and magnetic coupling via bridging ligand geometry in a bimetallic ytterbocene complex.

The ligand 1-methyl-3,5-bis(2,2':6',2' '-terpyridin-4'-yl)benzene has been employed in the synthesis of a new bimetallic ytterbocene complex [(Cp*)2Yb](1-methyl-3,5-bis(2,2':6',2' '-terpyridin-4'-yl)benzene)[Yb(Cp*)2] (1) and the doubly oxidized congener [1]2+ in an attempt to determine the impact of the bridging ligand geometry on the magnetic/electronic properties as compared to the previously reported 1,4-analog [(Cp*)2Yb](1,4-di(terpyridyl)benzene)[Yb(Cp*)2] (2). Electrochemical, electronic, and magnetic data provide compelling evidence that the 1,3-geometry associated with the bridging ligand of 1 has done an effective job of inhibiting electronic communication between metal centers and magnetic coupling of spin carriers at room temperature as compared to 2. In fact, the physical data associated with 1 are quite similar to those reported for the monometallic analog (Cp*)2Yb(tpy) (3).

1,4-Dihydroindeno[1,2-c]pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel.

The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po).

Systematic studies of early actinide complexes: thorium(IV) fluoroketimides.

Reaction of (C5Me5)2Th(CH3)2 with 2 equiv of NC-ArF gives the corresponding fluorinated thorium(IV) bis(ketimide) complexes (C5Me5)2Th[-N=C(CH3)(ArF)]2 (where ArF = 3-F-C6H4 (4), 4-F-C6H4 (5), 2-F-C6H4 (6), 3,5-F2-C6H3 (7), 3,4,5-F3-C6H2 (8), 2,6-F2-C6H3 (9), 2,4,6-F3-C6H2 (10), and C6F5 (11)). The complexes have been characterized by a combination of single-crystal X-ray diffraction, cyclic voltammetry and NMR, and UV-visible absorption and low-temperature luminescence spectroscopies. Density functional theory (DFT) and time-dependent DFT (TD-DFT) results are reported for complexes 5, 11, and (C5Me5)2Th[-N=C(Ph)2]2 (1) for comparison with experimental data and to guide in the interpretation of the spectroscopic results.

A survey of self-reported outcome instruments for the foot and ankle.

The information acquired from self-reported outcome instruments is useful only if there is evidence to support the interpretation of obtained scores. To properly interpret scores, there should be evidence for content validity, construct validity, reliability, and responsiveness. Evidence regarding score interpretation must also contain a description of the applicable test conditions, including information about the characteristics of subjects, timing of data collection, and construct of change.

The effects of plasma proteins on delayed repolarization in vitro with cisapride, risperidone, and D, L-sotalol.

Introduction: Drug-induced long QT syndrome (LQTS) has been linked to arrhythmias (including Torsades de Pointes and sudden cardiac death), and has led to an increased awareness of the potential risk of delayed repolarization in vitro and in vivo. However, in vitro assessments of delayed repolarization have not been fully predictive of in vivo effects.

Methods: To define the extent to which plasma protein binding (ppb) contributes to such disparities in repolarization studies, we compared drug-induced prolongation of the canine Purkinje fiber action potential duration (APD(90)) in vitro during superfusion with 100% Tyrode's solution (Tyrodes), canine plasma [50% plasma/50% Tyrodes] and a 5% solution of recombinant human serum albumin in Tyrodes (HSA).

Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor.

In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model.

Sealing properties of two contemporary single-cone obturation systems.

Aim: To compare the sealing of root canals filled with two single-cone obturation systems and a warm vertical compaction technique.

Methodology: Forty-two single-rooted teeth were decoronated to obtain 17-mm-long root segments. The root canals were cleaned and shaped to size 40, 0.