Granulocyte-Colony Stimulating Factor (G-CSF) Improves Motor Recovery in the Rat Impactor Model for Spinal Cord Injury

Granulocyte-colony stimulating factor (G-CSF) improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function

Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer

<p>Abstract</p> <p>Background</p> <p>Understanding what constitutes an important difference on a HRQL measure is critical to its interpretation. The aim of this study was to provide a range of estimates of minimally important differences (MIDs) in EQ-5D scores in cancer and to determine if estimates are comparable in lung cancer.</p> <p>Methods</p> <p>A retrospective analysis was conducted on cross-sectional data collected from 534 cancer patients, 50 of whom were lung cancer patients. A range of minimally important differences (MIDs) in EQ-5D index-based utility (UK and US) scores and VAS scores were estimated using both anchor-based and distribution-based (1/2 standard deviation and standard error of the measure) approaches. Groups were anchored using Eastern Cooperative Oncology Group performance status (PS) ratings and FACT-G total score-based quintiles.</p> <p>Results</p> <p>For UK-utility scores, MID estimates based on PS ranged from 0.10 to 0.12 both for all cancers and for lung cancer subgroup. Using FACT-G quintiles, MIDs were 0.09 to 0.10 for all cancers, and 0.07 to 0.08 for lung cancer. For US-utility scores, MIDs ranged from 0.07 to 0.09 grouped by PS for all cancers and for lung cancer; when based on FACT-G quintiles, MIDs were 0.06 to 0.07 in all cancers and 0.05 to 0.06 in lung cancer. MIDs for VAS scores were similar for lung and all cancers, ranging from 8 to 12 (PS) and 7 to 10 (FACT-G quintiles).</p> <p>Discussion</p> <p>Important differences in EQ-5D utility and VAS scores were similar for all cancers and lung cancer, with the lower end of the range of estimates closer to the MID, i.e. 0.08 for UK-index scores, 0.06 for US-index scores, and 0.07 for VAS scores.</p

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

The p53 Tumor Suppressor-Like Protein nvp63 Mediates Selective Germ Cell Death in the Sea Anemone Nematostella vectensis

Here we report the identification and molecular function of the p53 tumor suppressor-like protein nvp63 in a non-bilaterian animal, the starlet sea anemone Nematostella vectensis. So far, p53-like proteins had been found in bilaterians only. The evolutionary origin of p53-like proteins is highly disputed and primordial p53-like proteins are variably thought to protect somatic cells from genotoxic stress. Here we show that ultraviolet (UV) irradiation at low levels selectively induces programmed cell death in early gametes but not somatic cells of adult N. vectensis polyps. We demonstrate with RNA interference that nvp63 mediates this cell death in vivo. Nvp63 is the most archaic member of three p53-like proteins found in N. vectensis and in congruence with all known p53-like proteins, nvp63 binds to the vertebrate p53 DNA recognition sequence and activates target gene transcription in vitro. A transactivation inhibitory domain at its C-terminus with high homology to the vertebrate p63 may regulate nvp63 on a molecular level. The genotoxic stress induced and nvp63 mediated apoptosis in N. vectensis gametes reveals an evolutionary ancient germ cell protective pathway which relies on p63-like proteins and is conserved from cnidarians to vertebrates

Predicting sulfotyrosine sites using the random forest algorithm with significantly improved prediction accuracy

addresses: School of Biosciences, University of Exeter, Exeter EX4 5DE, UK. [email protected]: PMCID: PMC2777180types: Journal Article; Research Support, Non-U.S. Gov't© 2009 Yang; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Tyrosine sulfation is one of the most important posttranslational modifications. Due to its relevance to various disease developments, tyrosine sulfation has become the target for drug design. In order to facilitate efficient drug design, accurate prediction of sulfotyrosine sites is desirable. A predictor published seven years ago has been very successful with claimed prediction accuracy of 98%. However, it has a particularly low sensitivity when predicting sulfotyrosine sites in some newly sequenced proteins