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The World Health Organization (WHO) has identified the spread of antibiotic resistance as one of the major risks to global public health. An important transfer route into the aquatic environment is the urban water cycle. In this paper the occurrence and transport of antibiotic microbial resistance in the urban water cycle are critically reviewed. The presence of antibiotic resistance in low impacted surface water is being discussed to determine background antibiotic resistance levels, which might serve as a reference for treatment targets in the absence of health-based threshold levels. Different biological, physical and disinfection/oxidation processes employed in wastewater treatment and their efficacy regarding their removal of antibiotic resistant bacteria and antibiotic resistance geness (ARGs) were evaluated. A more efficient removal of antibiotic microbial resistance abundances from wastewater effluents can be achieved by advanced treatment processes, including membrane filtration, ozonation, UV-irradiation or chlorination, to levels typically observed in urban surface water or low impacted surface water.

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OBJECTIVE: To develop normative reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS) and KOOS-Child, as well as investigate socio-demographic, psychological and physical factors associated with knee pain and disability among healthy adults. METHOD: The KOOS or KOOS-Child (each containing five subscales) was administered to participants aged 8-101 years within the 1000 Norms Project, an observational study of 1000 self-reported healthy individuals. Self-efficacy, physical activity, body mass index (BMI), lower limb alignment, knee frontal plane projection angle (FPPA), knee range of motion (ROM), knee and hip strength, six-minute walk, 30-second chair stand and timed up and down stairs tests were collected. KOOS data were dichotomised using established cut-off scores and logistic regression analyses were conducted for each subscale. RESULTS: Socio-demographic characteristics were similar to the Australian population. Normative reference data were generated for children (8-17 years) and adults (18-101 years). Female adults were up to twice as likely to report knee pain, symptoms and sport/recreation (Sport/Rec) limitations compared to males (P < .05). Older age, lower self-efficacy, greater BMI, varus lower limb alignment, lower knee flexion ROM and lower hip external rotation (ER) strength were independently associated with knee pain and disability among adults. CONCLUSIONS: Age- and gender-stratified reference data for the KOOS and KOOS-Child have been developed to guide interpretation of results in practice and research for individuals with knee disorders. Psychological and physical factors are linked with self-reported knee pain/disability among adults, and longitudinal studies to investigate causation are required.

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The purpose of this original investigation was to determine if selected sensorimotor, mechanical, and self-reported measures are different among chronic ankle instability (CAI) subgroups, healthy control participants, and lateral ankle sprain copers (LAS-Copers). Ninety-four participants volunteered and were categorized into perceived ankle instability (PI) alone (n = 13), recurrent ankle sprains (RAS) alone (n = 12), PI in combination with RAS (PI-RAS; n = 25), LAS-Copers (n = 18), and controls (n = 26). Participants completed self-assessed global, regional, and psychological health-related quality-of-life (HRQOL) questionnaires and assessments of sensorimotor function and mechanical joint laxity. One-way ANOVAs were performed with the intention of reducing the number of original outcomes into a smaller number of predictor variables. Discriminant functional analysis was used to establish which specific measures best differentiate between groups. Eight outcome measures from neural excitability, postural control, static postural control, and HRQOL showed a significant differentiation between five groups (Wilk's λ = 0.26, χ232  = 114 45, P < 0.001, canonical correlation = 0.80) and correctly determined only 58.1% of group membership, and the PI-RAS and control groups were the only fit in the proposed model. A different model or other sensorimotor outcomes from more dynamic and complex tasks may be needed for the PI, RAS, and LAS-Coper groups.

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AIM: To compare the cleaning effectiveness and shaping ability of Mtwo, PVD-coated and uncoated EasyShape nickel-titanium rotary instruments during the preparation of curved root canals in extracted human teeth. METHODOLOGY: A total of 60 root canals of mandibular and maxillary molars with curvatures ranging between 25° and 35° were divided into three groups of 20 canals. Based on radiographs taken prior to instrumentation with the initial instrument inserted into the canal, the groups were balanced with respect to the angle and the radius of canal curvature. Canals were prepared using a low-torque control motor according the single-length technique. Using pre- and post-instrumentation radiographs, straightening of the canal curvatures was determined with a computer image analysis program. Preparation time, changes of working length and instrument failures were also recorded. These data were analysed statistically using ANOVA and Student-Newman-Keuls test. The amounts of debris and smear layer were quantified on the basis of a numerical evaluation scale. The data established for scoring the debris and the smear layer were recorded separately and analysed statistically using the Kruskal-Wallis test. RESULTS: During preparation, one coated and two uncoated EasyShape files fractured. Completely clean root canals were never observed. All instruments maintained the original canal curvature well with no significant differences between the different instruments (P > 0.05). Instrumentation with Mtwo files was significantly faster than with the two other instruments (P < 0.05). For debris removal Mtwo instruments achieved significantly better results (P < 0.001) than the two EasyShape instruments. The use of coated EasyShape files resulted in significantly less debris compared to instrumentation with uncoated EasyShape instruments (P < 0.05). The results for remaining smear layer were similar and not significantly different for the coronal, middle and apical third of the canals (P > 0.05) but in summary significantly less smear layer was observed following instrumentation with Mtwo (P < 0.01). CONCLUSIONS: Under the conditions of this study, all instruments maintained the original canal curvature well. The use of Mtwo instruments resulted in good canal cleanliness. PVD-coating of EasyShape instruments had no impact on their shaping ability but improved their cleaning effectiveness.

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Herpesvirus saimiri can be used as an efficient gene expression vector for human T lymphocytes and thus may allow applications in experimental leukemia therapy. We constructed recombinant viruses for the functional expression of the thymidine kinase (TK) of herpes simplex virus type 1 (HSV) as a suicide gene. These viruses reliably allowed the targeted elimination of transduced nonpermissive human T cells in vitro after the administration of ganciclovir. To test the reliability of this function under the most stringent permissive conditions, in this study we analyzed the influence of the prodrugs ganciclovir and acyclovir in common marmosets on the acute leukemogenesis induced by either wild-type herpesvirus saimiri C488 or by a recombinant derivative expressing TK of HSV. Antiviral drug treatment did not influence the rapid development of acute disease. In contrast, the presence of the HSV tk gene resulted in a faster disease progression. In addition, HSV TK-expressing viruses showed faster replication than wild-type virus in culture at low serum concentrations. Thus, HSV TK accelerates the replication of herpesvirus saimiri and enhances its pathogenicity. This should be generally considered when HSV TK is applied as a transgene in replication-competent DNA virus vectors for gene therapy.

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Herpesvirus saimiri transforms human T lymphocytes to stable growth and persists episomally without genomic integration and without virus production. The transformed T cells retain essential features of their parental cells including the MHC-restricted antigen specificity which may be useful for applications in adoptive immunotherapy. In order to improve the biological safety of such vectors, the prodrug activating gene thymidine kinase of herpes simplex virus was inserted into the genome of herpesvirus saimiri by homologous recombination. After infection with wild-type or cloned recombinant viruses, T cells from tamarin monkeys and from humans were transformed to stable growth. Thymidine kinase-expressing transformed T cells were efficiently eliminated in the presence of low concentrations of ganciclovir. This elimination mechanism remained fully functional over an observation period of 12 months. The potentially immunogenic neomycin resistance gene expression cassette was deleted from the genome of established mutant viruses by using the prokaryotic Cre/LoxP recombination system. At any time during the course of a therapeutic application, thymidine kinase-expressing transformed human T cells might be eliminated after administration of ganciclovir. In principle, this function could be useful for the T cell-dependent immunotherapy of resistant blood cancer while avoiding the risk of uncontrolled graft-versus-host disease.

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If structural knowledge of a receptor under consideration is lacking, drug design approaches focus on similarity or dissimilarity analysis of putative ligands. In this context the mutual ligand superposition is of utmost importance. Methods that are rapid enough to facilitate interactive usage, that allow to process sets of conformers and that enable database screening are of special interest here. The ability to superpose molecular fragments instead of entire molecules has proven to be helpful too. The RIGFIT approach meets these requirements and has several additional advantages. In three distinct test applications, we evaluated how closely we can approximate the observed relative orientation for a set of known crystal structures, we employed RIGFIT as a fragment placement procedure, and we performed a fragment-based database screening. The run time of RIGFIT can be traded off against its accuracy. To be competitive in accuracy with another state-of-the-art alignment tool, with which we compare our method explicitly, computing times of about 6 s per superposition on a common day workstation are required. If longer run times can be afforded the accuracy increases significantly. RIGFIT is part of the flexible superposition software FLEXS which can be accessed on the WWW [http:/(/)cartan.gmd.de/FlexS].

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In comparison to wild-type herpesvirus saimiri, viral interleukin-17 gene knockout mutants have unaltered behavior regarding viral replication, T-cell transformation in vitro, and pathogenicity in cottontop tamarins. Thus, this gene is not required for T-cell lymphoma induction but may contribute to apathogenic viral persistence in the natural host, the squirrel monkey.

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The immediate-early gene ie14/vsag of herpesvirus saimiri has homology with murine superantigens. We compared the pathogenesis of infection with either ie14/vsag deletion mutants or wild-type virus C488 in cottontop tamarin monkeys (Saguinus oedipus). Two weeks after infection, all animals developed acute T-cell lymphomas independently of the presence of the viral ie14/vsag gene.

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Herpesvirus saimiri C488 transforms human T lymphocytes to stable growth in culture. The growth-transformed human T cells harbor the viral genome in a nonintegrated episomal form without production of virus particles. In these cells, virus gene expression was previously found to be confined to the transforming genes stpC and tip. In order to analyze virus gene expression in more detail, we applied a subtractive hybridization technique and compared stimulated virus-transformed cells with uninfected parental T cells of the same donor. A number of known T-cell activation genes were isolated. Viral stpC/tip cDNAs were enriched after subtraction. In addition, the viral immediate-early, superantigen-homologous gene ie14/vsag was represented by numerous cDNA clones that comprised the entire spliced transcript. Whereas a weak basal expression of ie14/vsag was detected by reverse transcription-PCR only, the phorbol ester-induced transcripts were readily shown by Northern blotting. ie14/vsag, which before had been classified as a major immediate-early gene of herpesvirus saimiri, is localized within a highly conserved region with extensive homologies to the cellular genome. Mutant viruses without the ie14/vsag gene are replication competent and fully capable of transforming human and marmoset T cells. Since ie14/vsag is transiently expressed after stimulation, it may increase T-cell proliferation in an activation-dependent and superantigen-like but apparently Vbeta-independent way.

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Albuterol is a beta2-adrenergic agonist commonly used as a bronchodilator for the treatment of patients with asthma. We have developed an assay to determine plasma levels as low as 50 pg/ml of albuterol by gas chromatography-mass spectrometry (GC-MS). This assay utilizes isotopically labeled albuterol ([13C]albuterol) as an internal standard. In this assay albuterol and the internal standard are recovered from 1 ml of plasma using solid-phase extraction. The samples are then derivatized to trimethylsilyl ethers using N,O-bis(trimethylsilyl)trifluoro-acetamide with 1% trimethylchlorosilane. The samples are then analyzed by GC-MS with selected-ion monitoring (SIM) for the ions m/z 369.15 and 370.15. The method has been validated for a concentration range of 50-10000 pg/ml in plasma.

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Comparisons of the spectroscopic properties of a number of Ru(III) complexes of imidazole ligands provide methods of distinguishing between various types of bonding that can occur in proteins and nucleic acids. In particular, EPR and (1)H NMR parameters arising from the paramagnetism of Ru(III) should aid in determining binding sites of Ru(III) drugs in macromolecules. Electrochemical studies on several imidazole complexes of ruthenium suggest that imidazole may serve as a significant pi-acceptor ligand in the presence of anionic ligands. Crystal structures are reported on two active immunosuppressant complexes. cis-[(Im)(2)(NH(3))(4)Ru(III)]Br(3) crystallizes in the triclinic space group P&onemacr; (No. 2) with the cell parameters a = 8.961(2) Å, b = 12.677(3) Å, c = 7.630(2) Å, alpha = 98.03(2) degrees, beta = 100.68(2) degrees, gamma = 81.59(2) degrees, and Z = 2 (R = 0.044). [(1MeIm)(6)Ru(II)]Cl(2).2H(2)O crystallizes in the monoclinic space group P2(1)/n (No. 14) with the cell parameters a = 7.994(2) Å, b = 13.173(4) Å, c = 14.904(2) Å, beta = 97.89(1) degrees, and Z = 2 (R = 0.052). The average Ru(II)-N bond distance is 2.106(8) Å.

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Las filarias continúan siendo un serio problema de salud a nivel mundial. Las siete especies de fialrias que infectan al hombre (Wucheria bancrofti, Brugía malayi,Onchocerca volvulus, Loa loa, Mansonella ozzardi) afectan alrededor de 100 de personas a nivel mundial. El control de las filariasis se ha orientado fundamentalmente a la eliminación de los insectos vectores y a la disminución de la transmisión de la infección usando agentes quimioterapéuticos o quimioprofilácticos. Si bien estas medidas han logrado disminuir la transmisión de las filarias, es probable que para lograr un control definitivo se requiera el desarrollo de vacunas...

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Parathyroid tissue that is stored for replantation purposes is usually kept in a special tank containing fluid nitrogen at -196 degrees C. Our studies demonstrate that storage is also possible in a deep-freezer at -70 degrees C without any loss of quality. Most hospitals own such freezers for storing bone marrow cells at the same temperature. Parathyroid tissue of 11 patients who were operated on because of primary hyperparathyroidism was stored in this way. After six months the tissue showed 75.7% morphologically intact cells. The control group's tissue was stored in liquid nitrogen according to the common method; after the same period of time it showed 76% histologically normal cells.

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The primary structure of the NADPH-protochlorophyllide oxidoreductase of barley has been deduced from the nucleotide sequence of a cloned full-length cDNA. This cDNA hybridizes to a 1.7 kb RNA whose steady-state level in dark-grown seedlings is drastically reduced upon illumination. The predicted amino acid sequence (388 residues in length) includes a transit peptide of 74 amino acids whose end point has been delimited by sequencing the N-terminus of the mature protein. Expression of the cDNA in Escherichia coli leads to the synthesis of an enzymatically active precursor of the NADPH-protochlorophyllide oxidoreductase. Activity of this protein in bacterial lysates is completely dependent on the presence of NADPH and protochlorophyllide and requires light.

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A novel class of highly abundant polypeptides with antifungal activity has been detected in cell walls of barley leaves. Similar polypeptides known as thionins occur not only in monocotyledonous but also in various dictoyledonous plants. The leaf-specific thionins of barley are encoded by a complex multigene family, which consists of at least 50-100 members per haploid genome. All of these genes are confined to chromosome 6. The toxicity of these thionins for plant pathogenic fungi and the fact that their synthesis can also be triggered by pathogens strongly suggest that thionins are a naturally occurring, inducible plant protein possibly involved in the mechanism of plant defence against microbial infections.

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Urticarial vasculitis is a syndrome characterized by a chronic intermittent urticaria and the histological features of necrotizing vasculitis. The skin lesions are often accompanied by arthritis or arthralgia and other systemic diseases. Depressed serum complement can be found in half of the patients.

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