999 resultados para RNA, Guide


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Elderly people are prone to drug-induced adverse events (AEs), which often manifest as an atypical clinical picture. The differential diagnosis of any new symptom or alteration in the general state of health in the elderly must, therefore, include AEs. This article offers a practical tool designed to help clinicians to rapidly identify which drugs may induce which kind of frequent symptoms or syndromes.

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Machado-Joseph disease or Spinocerebellar ataxia type 3 is a progressive fatal neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Recent studies demonstrate that RNA interference is a promising approach for the treatment of Machado-Joseph disease. However, whether gene silencing at an early time-point is able to prevent the appearance of motor behavior deficits typical of the disease when initiated before onset of the disease had not been explored. Here, using a lentiviral-mediated allele-specific silencing of mutant ataxin-3 in an early pre-symptomatic cerebellar mouse model of Machado-Joseph disease we show that this strategy hampers the development of the motor and neuropathological phenotypic characteristics of the disease. At the histological level, the RNA-specific silencing of mutant ataxin-3 decreased formation of mutant ataxin-3 aggregates, preserved Purkinje cell morphology and expression of neuronal markers while reducing cell death. Importantly, gene silencing prevented the development of impairments in balance, motor coordination, gait and hyperactivity observed in control mice. These data support the therapeutic potential of RNA interference for Machado-Joseph disease and constitute a proof of principle of the beneficial effects of early allele-specific silencing for therapy of this disease.

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Collection : Bibliothèque de la maîtresse de maison

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The efficacy and safety of anti-infective treatments are associated with the drug blood concentration profile, which is directly correlated with a dosing adjustment to the individual patient's condition. Dosing adjustments to the renal function recommended in reference books are often imprecise and infrequently applied in clinical practice. The recent generalisation of the KDOQI (Kidney Disease Outcome Quality Initiative) staging of chronically impaired renal function represents an opportunity to review and refine the dosing recommendations in patients with renal insufficiency. The literature has been reviewed and compared to a predictive model of the fraction of drug cleared by the kidney based on the Dettli's principle. Revised drug dosing recommendations integrating these predictive parameters are proposed.

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[Expos. internat.. Paris. 1937]

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The current 1993 American Association of State Highway and Transportation Officials (AASHTO) Pavement Design Guide is based on the empirical interpretation of the results of the 1960 AASHTO Road Test. With the release of the new Mechanistic-Empirical (M-E) Pavement Design Guide, pavement design has taken a "quantum" leap forward. In order to effectively and efficiently transition to the M-E Pavement Design Guide, state DOTs need a detailed implementation and training strategy. This document is a plan for the M-E Pavement Design Guide to be implemented in Iowa.

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The performance of a pavement depends on the quality of its subgrade and subbase layers; these foundational layers play a key role in mitigating the effects of climate and the stresses generated by traffic. Therefore, building a stable subgrade and a properly drained subbase is vital for constructing an effective and long lasting pavement system. This manual has been developed to help Iowa highway engineers improve the design, construction, and testing of a pavement system’s subgrade and subbase layers, thereby extending pavement life. The manual synthesizes current and previous research conducted in Iowa and other states into a practical geotechnical design guide [proposed as Chapter 6 of the Statewide Urban Design and Specifications (SUDAS) Design Manual] and construction specifications (proposed as Section 2010 of the SUDAS Standard Specifications) for subgrades and subbases. Topics covered include the important characteristics of Iowa soils, the key parameters and field properties of optimum foundations, embankment construction, geotechnical treatments, drainage systems, and field testing tools, among others.

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This research project investigated the effects of concentrated brines of magnesium chloride, calcium chloride, sodium chloride, and calcium magnesium acetate on portland cement concrete. Although known to be effective at deicing and anti-icing, the deleterious effects these chemicals may have on concrete have not been well documented. As a result of this research, it was determined that there is significant evidence that magnesium chloride and calcium chloride chemically interact with hardened portland cement paste in concrete resulting in expansive cracking, increased permeability, and a significant loss in compressive strength. Although the same effects were not seen with sodium chloride brines, it was shown that sodium chloride brines have the highest rate of ingress into hardened concrete. This latter fact is significant with respect to corrosion of embedded steel. The mechanism for attack of hardened cement paste varies with deicer chemical but in general, a chemical reaction between chlorides and cement hydration products results in the dissolution of the hardened cement paste and formation of oxychloride phases, which are expansive. The chemical attack of the hardened cement paste is significantly reduced if supplementary cementitious materials are included in the concrete mixture. Both coal fly ash and ground granulated blast furnace slag were found to be effective at mitigating the chemical attack caused by the deicers tested. In the tests performed, ground granulated blast furnace slag performed better as a mitigation strategy as compared to coal fly ash. Additionally, siloxane and silane sealants were effective at slowing the ingress of deicing chemicals into the concrete and thereby reducing the observed distress. In general, the siloxane sealant appeared to be more effective than the silane, but both were effective and should be considered as a maintenance strategy.