Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1

Alzheimer's disease (AD) afflicts around 20 million people worldwide and so there is an urgent need for effective treatment. Our research showing that herpes simplex virus type 1 (HSV1) is a risk factor for AD for the brains of people who possess a specific genetic factor and that the virus causes accumulation of key AD proteins (β-amyloid (Aβ) and abnormally phosphorylated tau (P-tau)), suggests that anti-HSV1 antiviral agents might slow AD progression. However, currently available antiviral agents target HSV1 DNA replication and so might be successful in AD only if Aβ and P-tau accumulation depend on viral DNA replication. Therefore, we investigated firstly the stage(s) of the virus replication cycle required for Aβ and P-tau accumulation, and secondly whether antiviral agents prevent these changes using recombinant strains of HSV1 that progress only partly through the replication cycle and antiviral agents that inhibit HSV1 DNA replication. By quantitative immunocytochemistry we demonstrated that entry, fusion and uncoating of HSV1, are insufficient to induce Aβ and P-tau production. We showed also that none of the “immediate early” viral proteins is directly responsible, and that Aβ and P-tau are produced at a subsequent stage of the HSV1 replication cycle. Importantly, the anti-HSV1 antiviral agents acyclovir, penciclovir and foscarnet reduced Aβ and P-tau accumulation, as well as HSV1, with foscarnet being less effective in each case. P-tau accumulation was found to depend on HSV1 DNA replication, whereas Aβ accumulation was not. The antiviral-induced decrease in Aβ is attributable to the reduced number of new viruses, and hence the reduction in viral spread. Since antiviral agents reduce greatly Aβ and P-tau accumulation in HSV1-infected cells, they would be suitable for treating AD with great advantage unlike current AD therapies, only the virus, not the host cell, would be targeted

The cost-effectiveness of a new disease management model for frail elderly living in homes for the elderly, design of a cluster randomized controlled clinical trial

<p>Abstract</p> <p>Background</p> <p>The objective of this article is to describe the design of a study to evaluate the clinical and economic effects of a Disease Management model on functional health, quality of care and quality of life of persons living in homes for the elderly.</p> <p>Methods</p> <p>This study concerns a cluster randomized controlled clinical trial among five intervention homes and five usual care homes in the North-West of the Netherlands with a total of over 500 residents. All persons who are not terminally ill, are able to be interviewed and sign informed consent are included. For cognitively impaired persons family proxies will be approached to provide outcome information. The Disease Management Model consists of several elements: (1) Trained staff carries out a multidimensional assessment of the patients functional health and care needs with the interRAI Long Term Care Facilities instrument (LTCF). Computerization of the LTCF produces immediate identification of problem areas and thereby guides individualized care planning. (2) The assessment outcomes are discussed in a Multidisciplinary Meeting (MM) with the nurse, primary care physician, nursing home physician and Psychotherapist and if necessary other members of the care team. The MM presents individualized care plans to manage or treat modifiable disabilities and risk factors. (3) Consultation by an nursing home physician and psychotherapist is offered to the frailest residents at risk for nursing home admission (according to the interRAI LTCF). Outcome measures are Quality of Care indicators (LTCF based), Quality Adjusted Life Years (Euroqol), Functional health (SF12, COOP-WONCA), Disability (GARS), Patients care satisfaction (QUOTE), hospital and nursing home days and mortality, health care utilization and costs.</p> <p>Discussion</p> <p>This design is unique because no earlier studies were performed to evaluate the effects and costs of this Disease Management Model for disabled persons in homes for the elderly on functional health and quality of care.</p> <p>Trail registration number</p> <p>ISRCTN11076857</p

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Congregation Am Echod (Waukegan, Ill.) minute book 1896-1901

Contains the by-laws, official minutes of meetings, and financial records in Yiddish of the synagogu

Automatic urban debris zone extraction from post-hurricane very high-resolution satellite and aerial imagery

Automated remote sensing methods have not gained widespread usage for damage assessment after hurricane events, especially for low-rise buildings, such as individual houses and small businesses. Hurricane wind, storm surge with waves, and inland flooding have unique damage signatures, further complicating the development of robust automated assessment methodologies. As a step toward realizing automated damage assessment for multi-hazard hurricane events, this paper presents a mono-temporal image classification methodology that quickly and accurately differentiates urban debris from non-debris areas using post-event images. Three classification approaches are presented: spectral, textural, and combined spectral–textural. The methodology is demonstrated for Gulfport, Mississippi, using IKONOS panchromatic satellite and NOAA aerial colour imagery collected after 2005 Hurricane Katrina. The results show that multivariate texture information significantly improves debris class detection performance by decreasing the confusion between debris and other land cover types, and the extracted debris zone accurately captures debris distribution. Additionally, the extracted debris boundary is approximately equivalent regardless of imagery type, demonstrating the flexibility and robustness of the debris mapping methodology. While the test case presents results for hurricane hazards, the proposed methodology is generally developed and expected to be effective in delineating debris zones for other natural hazards, including tsunamis, tornadoes, and earthquakes

The castle by the sea = Das Schloss am Meere /

First line of poem: Hast thou seen that lordly castle.First line of text: Hast seen that lordly castle.Cover illustration: engraving of castle by the sea / Stackpole.Dedicated to: Dr. F. Zinsser.German text, parallel English translation.From poem: The castle by the sea / Henry Wadsworth Longfellow. Cf. Poetical works of Longfellow, Cambridge ed., 1975, p. 611. Translated from poem: Das Schloss am Meere / Ludwig Uhland.Cover title.For voice and piano.BAL,Mode of access: Internet.From the Thomas A. Edison Collection of American Sheet Music