Are citations from clinical trials evidence of higher impact research? An analysis of ClinicalTrials.gov

An important way in which medical research can translate into improved health outcomes is by motivating or influencing clinical trials that eventually lead to changes in clinical practice. Citations from clinical trials records to academic research may therefore serve as an early warning of the likely future influence of the cited articles. This paper partially assesses this hypothesis by testing whether prior articles referenced in ClinicalTrials.gov records are more highly cited than average for the publishing journal. The results from four high profile general medical journals support the hypothesis, although there may not be a cause-and effect relationship. Nevertheless, it is reasonable for researchers to use citations to their work from clinical trials records as partial evidence of the possible long-term impact of their research

Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ(2)

BACKGROUND: The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of reactive oxygen species. The cytotoxic effects of hydrogen peroxide (H(2)O(2)) induced oxidative stress on retinal pigment epithelium were characterized in this study. METHODS: The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line. RESULTS: The treatment of retinal pigment epithelial cells with H(2)O(2 )caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the prostaglandin derivative, 15d-PGJ(2 )and by the protein kinase inhibitor, AG126. CONCLUSION: 15d-PGJ(2 )and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases

In Vivo Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers

DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987

The Whereabouts of an Ancient Wanderer: Global Phylogeography of the Solitary Ascidian Styela plicata

Genetic tools have greatly aided in tracing the sources and colonization history of introduced species. However, recurrent introductions and repeated shuffling of populations may have blurred some of the genetic signals left by ancient introductions. Styela plicata is a solitary ascidian distributed worldwide. Although its origin remains unclear, this species is believed to have spread worldwide by travelling on ship's hulls. The goals of this study were to infer the genetic structure and global phylogeography of S. plicata and to look for present-day and historical genetic patterns. Two genetic markers were used: a fragment of the mitochondrial gene Cytochrome Oxidase subunit I (COI) and a fragment of the nuclear gene Adenine Nucleotide Transporter/ADP-ATP Translocase (ANT). A total of 368 individuals for COI and 315 for ANT were sequenced from 17 locations worldwide. The levels of gene diversity were moderate for COI to high for ANT. The Mediterranean populations showed the least diversity and allelic richness for both markers, while the Indian, Atlantic and Pacific Oceans had the highest gene and nucleotide diversities. Network and phylogenetic analyses with COI and ANT revealed two groups of alleles separated by 15 and 4 mutational steps, respectively. The existence of different lineages suggested an ancient population split. However, the geographic distributions of these groups did not show any consistent pattern, indicating different phylogeographic histories for each gene. Genetic divergence was significant for many population-pairs irrespective of the geographic distance among them. Stochastic introduction events are reflected in the uneven distribution of COI and ANT allele frequencies and groups among many populations. Our results confirmed that S. plicata has been present in all studied oceans for a long time, and that recurrent colonization events and occasional shuffling among populations have determined the actual genetic structure of this species

MRI compared to conventional diagnostic work-up in the detection and evaluation of invasive lobular carcinoma of the breast: a review of existing literature

Item does not contain fulltextPURPOSE: The clinical diagnosis and management of invasive lobular carcinoma (ILC) of the breast presents difficulties. Magnetic resonance imaging (MRI) has been proposed as the imaging modality of choice for the evaluation of ILC. Small studies addressing different aspects of MRI in ILC have been presented but no large series to date. To address the usefulness of MRI in the work-up of ILC, we performed a review of the currently published literature. MATERIALS AND METHODS: We performed a literature search using the query "lobular AND (MRI OR MR OR MRT OR magnetic)" in the Cochrane library, PubMed and scholar.google.com, to retrieve all articles that dealt with the use of MRI in patients with ILC. We addressed sensitivity, morphologic appearance, correlation with pathology, detection of additional lesions, and impact of MRI on surgery as different endpoints. Whenever possible we performed meta-analysis of the pooled data. RESULTS: Sensitivity is 93.3% and equal to overall sensitivity of MRI for malignancy in the breast. Morphologic appearance is highly heterogeneous and probably heavily influenced by interreader variability. Correlation with pathology ranges from 0.81 to 0.97; overestimation of lesion size occurs but is rare. In 32% of patients, additional ipsilateral lesions are detected and in 7% contralateral lesions are only detected by MRI. Consequently, MRI induces change in surgical management in 28.3% of cases. CONCLUSION: This analysis indicates MRI to be valuable in the work-up of ILC. It provides additional knowledge that cannot be obtained by conventional imaging modalities which can be helpful in patient treatment

Intestinal infection with Mycobacterium avium in acquired immune deficiency syndrome (AIDS)

At endoscopy, a 30-year-old man with acquired immune deficiency syndrome (AIDS), Kaposi's sarcoma, diarrhea, and unexplained malabsorption showed erythematous macular duodenal lesions consistent with Whipple's disease by histology and electron microscopy. Symptoms did not respond to tetracycline. Subsequent cultures revealed systemic Mycobacterium avium (M. avium) infection. Tissue from this patient, from patients with Whipple's disease and from a macaque with M. avium were compared. All contained PAS-positive macrophages but M. avium could be distinguished by positive acid-fast stains and a difference in pattern of indirect immunofluorescence staining with bacterial typing antisera. PAS-positive macrophages in the intestinal lamina propria are no longer pathognomonic of Whipple's disease. Ultrastructural and histological similarities between Whipple's disease and M. avium infection suggest that both are manifestations of immune deficits limiting macrophage destruction of particular bacteria after phagocytosis. M. avium must be considered in the differential diagnosis of diarrhea in patients with AIDS and other immunosuppressed conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44396/1/10620_2005_Article_BF01318186.pd

Interactions between metal ions and DNA

84 years elapsed between the announcements of the periodic table and that of the DNA double helix in 1953, and the two have been combined in many ways since then. In this chapter an outline of the fundamentals of DNA structure leads into a range of examples showing how the natural magnesium and potassium ions found in nature can be substituted in a diversity of applications. The dynamic structures found in nature have been studied in the more controlled but artificial environment of the DNA crystal using examples from sodium to platinum and also in a range of DNA-binding metal complexes. While NMR is an essential technique for studying nucleic acid structure and conformation, most of our knowledge of metal ion binding has come from X-ray crystallography. These days the structures studied, and therefore also the diversity of metal binding, go beyond the double helix to triplexes, hairpin loops, junctions and quadruplexes, and the chapter describes briefly how these pieces fit into the DNA jigsaw. In a final section, the roles of metal cations in the crystallisation of new DNA structures are discussed, along with an introduction to the versatility of the periodic table of absorption edges for nucleic acid structure determination