1,169 research outputs found

    An Explanation of the Action of the House of Delegates*

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    Targeted anthelmintic treatment of parasitic gastroenteritis in first grazing season dairy calves using daily live weight gain as an indicator

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    Control of parasitic gastroenteritis in cattle is typically based on group treatments with anthelmintics, complemented by grazing management, where feasible. However, the almost inevitable evolution of resistance in parasitic nematodes to anthelmintics over time necessitates a reappraisal of their use in order to reduce selection pressure. One such approach is targeted selective treatment (TST), in which only individual animals that will most benefit are treated, rather than whole groups of at-risk cattle. This study was designed to assess the feasibility of implementing TST on three commercial farms, two of which were organic. A total of 104 first-grazing season (FGS), weaned dairy calves were enrolled in the study; each was weighed at monthly intervals from the start of the grazing season using scales or weigh-bands. At the same time dung and blood samples were collected in order to measure faecal egg counts (FEC) and plasma pepsinogen, respectively. A pre-determined threshhold weight gain of 0.75 kg/day was used to determine those animals that would be treated; the anthelmintic used was eprinomectin. No individual animal received more than one treatment during the grazing season and all treatments were given in July or August; five animals were not treated at all because their growth rates consistently exceeded the threshold. Mean daily live weight gain over the entire grazing season ranged between 0.69 and 0.82 kg/day on the three farms. Neither FEC nor pepsinogen values were significantly associated with live weight gain. Implementation of TST at farm level requires regular (monthly) handling of the animals and the use of weigh scales or tape, but can be integrated into farm management practices. This study has shown that acceptable growth rates can be achieved in FGS cattle with modest levels of treatment and correspondingly less exposure of their nematode populations to anthelmintics, which should mitigate selection pressure for resistance by increasing the size of the refugia in both hosts and pasture

    Antenatal corticosteroids for fetal lung maturation: an overview of Cochrane reviews

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    This is the protocol for a review and there is no abstract. The objectives are as follows: The objective is to summarise the available evidence from Cochrane systematic reviews for the effectiveness and safety of antenatal corticosteroid therapy to improve infant outcomes

    Identification of Oxidized Protein Hydrolase as a Potential Prodrug Target in Prostate Cancer

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    Background: Esterases are often overexpressed in cancer cells and can have chiral specificities different from that of the corresponding normal tissues. For this reason, ester prodrugs could be a promising approach in chemotherapy. In this study, we focused on the identification and characterization of differentially expressed esterases between non-tumorigenic and tumorigenic prostate epithelial cells.Methods: Cellular lysates from LNCaP, DU 145, and PC3 prostate cancer cell lines, tumorigenic RWPE-2 prostate epithelial cells, and non-tumorigenic RWPE-1 prostate epithelial cells were separated by native polyacrylamide gel electrophoresis (n-PAGE) and the esterase activity bands visualized using Ξ±-naphthyl acetate or Ξ±-naphthyl-N-acetylalaninate (ANAA) chiral esters and Fast Blue RR salt. The esterases were identified using nanospray LC/MS-MS tandem mass spectrometry and confirmed by Western blotting, native electroblotting, inhibition assays, and activity towards a known specific substrate. The serine protease/esterase oxidized protein hydrolase (OPH) was overexpressed in COS-7 cells to verify our results.Results: The major esterase observed with the ANAA substrates within the n-PAGE activity bands was identified as OPH. OPH (EC 3.4.19.1) is a serine protease/esterase and a member of the prolyl oligopeptidase family. We found that LNCaP lysates contained approximately 40% more OPH compared to RWPE-1 lysates. RWPE-2, DU145 and PC3 cell lysates had similar levels of OPH activity. OPH within all of the cell lysates tested had a chiral preference for the S-isomer of ANAA. LNCaP cells were stained more intensely with ANAA substrates than RWPE-1 cells and COS-7 cells overexpressing OPH were found to have a higher activity towards the ANAA and AcApNA than parent COS-7 cells.Conclusions: These data suggest that prodrug derivatives of ANAA and AcApNA could have potential as chemotherapeutic agents for the treatment of prostate cancer tumors that overexpress OPH

    Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

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    Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

    Proximal ulna stress fracture and stress reaction of the proximal radius associated with the use of crutches: a case report and literature review

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    We report a case of complete stress fracture of the ulna and stress reaction of the radius resulting from the use of crutches in an overweight patient with severe lower extremity arthritis. Plain radiograph showed an undisplaced complete fracture of the proximal metaphysis of the ulna. Magnetic resonance imaging (MRI) was performed to exclude a pathological cause in view of the unusual fracture site, which confirmed the plain radiographic findings and additionally demonstrated a stress reaction in the proximal radius. There are three cases of stress fracture of the ulnar diaphysis resulting from the use of crutches reported previously in the English literature and a further case of bilaterally symmetrical ulnar diaphysial fracture reported in the Danish literature. We report the first case of ulnar metaphysis stress fracture with concomitant stress reaction of the radius
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