28 research outputs found
In Vitro HPV-11 Infection of Human Foreskin
Study of the infectious process of human papillomavirus type 11 (HPV-11) has been facilitated by the discovery that HPV- 11 – infected neonatal human foreskin epithelium can proliferate as xenografts into condyloma-like growths within athymic nude mice. Here we describe detection of HPV-1 1 infection of neonatal human foreskin-derived keratinocytes, infected and cultured entirely in vitro, by use of the polymerase chain reaction and primers straddling the splice donor/ acceptor site of the most prevalent early gene HPV-11 transcript (E1∧E4). Expression of the E1∧E4 HPV-11 mRNA is abrogated by 60°C heat inactivation of the inoculum. HPV- 11 – infected foreskin explants continue to produce the E1∧E4 mRNA for up to 5 weeks in culture, and second-passage keratinocytes derived from infected explant outgrowths continue to produce the E1∧E4 mRNA. The in vitro system described here provides a new way to study HPV-11 infection and may be useful in evaluating early events of infection
Human responses to Florida red tides : policy awareness and adherence to local fertilizer ordinances
Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Science of The Total Environment 493 (2014): 898-909, doi:10.1016/j.scitotenv.2014.06.083.To mitigate the damages of natural hazards, policy responses can be beneficial only if they are
effective. Using a self-administered survey approach, this paper focuses on the adherence to
local fertilizer ordinances (i.e., county or municipal rules regulating the application of fertilizer
to private lawns or facilities such as golf courses) implemented in jurisdictions along the
southwest Florida coast in response to hazardous blooms of Florida red tides (Karenia brevis).
These ordinances play a role in the context of evolving programs of water pollution control at
federal, state, water basin, and local levels. With respect to policy effectiveness, while the
strength of physical linkages is of critical importance, the extent to which humans affected are
aware of and adhere to the relevant rules, is equally critical. We sought to understand the
public’s depth of understanding about the rationales for local fertilizer ordinances. Respondents
in Sarasota, Florida, were asked about their fertilizer practices in an area that has experienced
several major blooms of Florida red tides over the past two decades. A highly educated, older
population of 305 residents and “snowbirds” reported relatively little knowledge about a local
fertilizer ordinance, its purpose, or whether it would change the frequency, size, or duration of
red tides. This finding held true even among subpopulations that were expected to have more
interest in or to be more knowledgeable about harmful algal blooms. In the face of uncertain
science and environmental outcomes, and with individual motivations at odds with evolving
public policies, the effectiveness of local community efforts to decrease the impacts of red tides
may be compromised. Targeted social-science research on human perceptions about the risks of
Florida red tides and education about the rationales for potential policy responses is warranted.This work was funded under sponsorship of the National Science Foundation (NSF), awards
#1009106 and #1004181and the National Institute for Environmental Health Sciences (NIEHS),
award # R21ES017413-01A2. Fleming received support from the European Regional
Development Fund and European Social Fund (European Centre for Environment and Human
Health, University of Exeter Medical School)
The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2
Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701
Discovery of <i>N</i>‑(4-Fluoro-3-methoxybenzyl)-6-(2-(((2<i>S</i>,5<i>R</i>)‑5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)‑2<i>H</i>‑tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis
Matrix
metalloproteinase-13 (MMP-13) is a zinc-dependent protease
responsible for the cleavage of type II collagen, the major structural
protein of articular cartilage. Degradation of this cartilage matrix
leads to the development of osteoarthritis. We previously have described
highly potent and selective carboxylic acid containing MMP-13 inhibitors;
however, nephrotoxicity in preclinical toxicology species precluded
development. The accumulation of compound in the kidneys mediated
by human organic anion transporter 3 (hOAT3) was hypothesized as a
contributing factor for the finding. Herein we report our efforts
to optimize the MMP-13 potency and pharmacokinetic properties of non-carboxylic
acid leads resulting in the identification of compound <b>43a</b> lacking the previously observed preclinical toxicology at comparable
exposures