144 research outputs found

    Tooth-surface-specific Effects of Xylitol: Randomized Trial Results

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    The Xylitol for Adult Caries Trial was a three-year, double-blind, multi-center, randomized clinical trial that evaluated the effectiveness of xylitol vs. placebo lozenges in the prevention of dental caries in caries-active adults. The purpose of this secondary analysis was to investigate whether xylitol lozenges had a differential effect on cumulative caries increments on different tooth surfaces. Participants (ages 21-80 yrs) with at least one follow-up visit (n = 620) were examined at baseline, 12, 24, and 33 months. Negative binomial and zero-inflated negative binomial regression models were used to estimate incidence rate ratios (IRR) for xylitol’s differential effect on cumulative caries increments on root and coronal surfaces and, among coronal surfaces, on smooth (buccal and lingual), occlusal, and proximal surfaces. Participants in the xylitol arm developed 40% fewer root caries lesions (0.23 D2FS/year) than those in the placebo arm (0.38 D2FS/year; IRR = 0.60; 95% CI [0.44, 0.81]; p < .001). There was no statistically significant difference between xylitol and control participants in the incidence of smooth-surface caries (p = .100), occlusal-surface caries (p = .408), or proximal-surface caries (p = .159). Among these caries-active adults, xylitol appears to have a caries-preventive effect on root surfaces (ClinicalTrials.gov NCT00393055)

    Geometrical principles of homomeric β-barrels and β-helices: Application to modeling amyloid protofilaments

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    Examples of homomeric β-helices and β-barrels have recently emerged. Here we generalise the theory for the shear number in β-barrels to encompass β-helices and homomeric structures. We introduce the concept of the “β-strip”, the set of parallel or antiparallel neighbouring strands, from which the whole helix can be generated giving it n-fold rotational symmetry. In this context the shear number is interpreted as the sum around the helix of the fixed register shift between neighbouring identical β-strips. Using this approach we have derived relationships between helical width, pitch, angle between strand direction and helical axis, mass per length, register shift, and number of strands. The validity and unifying power of the method is demonstrated with known structures including α-haemolysin, T4 phage spike, cylindrin, and the HET-s(218-289) prion. From reported dimensions measured by X-ray fibre diffraction on amyloid fibrils the relationships can be used to predict the register shift and the number of strands within amyloid protofilaments. This was used to construct models of transthyretin and Alzheimer β(40) amyloid protofilaments that comprise a single strip of in-register β-strands folded into a “β-strip helix”. Results suggest both stabilisation of an individual β-strip helix as well as growth by addition of further β-strip helices involves the same pair of sequence segments associating with β-sheet hydrogen bonding at the same register shift. This association would be aided by a repeat sequence. Hence understanding of how the register shift (as the distance between repeat sequences) relates to helical dimensions, will be useful for nanotube design

    Results from the Xylitol for Adult Caries Trial (X-ACT)

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    Although caries is prevalent in adults, few preventive therapies have been tested in adult populations. This randomized clinical trial evaluated the effectiveness of xylitol lozenges in preventing caries in elevated caries-risk adults

    Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

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    <p>Abstract</p> <p>Background</p> <p>Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe.</p> <p>Methods</p> <p>Hospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated.</p> <p>Results</p> <p>Of the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4 hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4) respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain.</p> <p>Conclusions</p> <p>Data from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment.</p> <p>Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.</p

    The STAR MAPS-based PiXeL detector

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    The PiXeL detector (PXL) for the Heavy Flavor Tracker (HFT) of the STAR experiment at RHIC is the first application of the state-of-the-art thin Monolithic Active Pixel Sensors (MAPS) technology in a collider environment. Custom built pixel sensors, their readout electronics and the detector mechanical structure are described in detail. Selected detector design aspects and production steps are presented. The detector operations during the three years of data taking (2014-2016) and the overall performance exceeding the design specifications are discussed in the conclusive sections of this paper

    Antisense-Mediated Knockdown of NaV1.8, but Not NaV1.9, Generates Inhibitory Effects on Complete Freund's Adjuvant-Induced Inflammatory Pain in Rat

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    Tetrodotoxin-resistant (TTX-R) sodium channels NaV1.8 and NaV1.9 in sensory neurons were known as key pain modulators. Comparing with the widely reported NaV1.8, roles of NaV1.9 on inflammatory pain are poorly studied by antisense-induced specific gene knockdown. Here, we used molecular, electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide (AS ODN) targeting NaV1.8 and NaV1.9 on inflammatory pain. Following complete Freund's adjuvant (CFA) inflammation treatment, NaV1.8 and NaV1.9 in rat dorsal root ganglion (DRG) up-regulated mRNA and protein expressions and increased sodium current densities. Immunohistochemical data demonstrated that NaV1.8 mainly localized in medium and small-sized DRG neurons, whereas NaV1.9 only expressed in small-sized DRG neurons. Intrathecal (i.t.) delivery of AS ODN was used to down-regulate NaV1.8 or NaV1.9 expressions confirmed by immunohistochemistry and western blot. Unexpectedly, behavioral tests showed that only NaV1.8 AS ODN, but not NaV1.9 AS ODN could reverse CFA-induced heat and mechanical hypersensitivity. Our data indicated that TTX-R sodium channels NaV1.8 and NaV1.9 in primary sensory neurons played distinct roles in CFA-induced inflammatory pain and suggested that antisense oligodeoxynucleotide-mediated blocking of key pain modulator might point toward a potential treatment strategy against certain types of inflammatory pain

    No detection of methane on Mars from early ExoMars Trace Gas Orbiter observations

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    The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere, which-given methane's lifetime of several centuries-predicts an even, well mixed distribution of methane. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally
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