Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

<b>Background</b> The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.<p></p> <b>Methods</b> Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 ug per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.<p></p> <b>Results</b> At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p=0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p=0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.<p></p> <b>Conclusions</b> Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma. Clinicaltrials.gov identifier: NCT0046382

Differentiating Non-Motor Symptoms in Parkinson's Disease from Controls and Hemifacial Spasm

10.1371/journal.pone.0049596PLoS ONE82

Molecular motors robustly drive active gels to a critically connected state

Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

Chemical Composition and Larvicidal Activities of the Himalayan Cedar, Cedrus deodara Essential Oil and Its Fractions Against the Diamondback Moth, Plutella xylostella

Plants and plant-derived materials play an extremely important role in pest management programs. Essential oil from wood chips of Himalayan Cedar, Cedrus deodara (Roxburgh) Don (Pinales: Pinaceae), was obtained by hydrodistillation and fractionated to pentane and acetonitrile from which himachalenes and atlantones enriched fractions were isolated. A total of forty compounds were identified from these fractions using GC and GC-MS analyses. Essential oils and fractions were evaluated for insecticidal activities against second instars of the diamondback moth, Plutella xylostella L. (Lepidoptera: Yponomeutidae), using a leaf dip method. All samples showed promising larvicidal activity against larvae of P. xylostella. The pentane fraction was the most toxic with a LC50 value of 287 µg/ml. The himachalenes enriched fraction was more toxic (LC50 = 362 µg/ml) than the atlantones enriched fraction (LC50 = 365 µg/ml). LC50 of crude oil was 425 µg/ml and acetonitrile fraction was LC50 = 815 µg/ml. The major constituents, himachalenes and atlantones, likely accounted for the insecticidal action. Present bioassay results revealed the potential for essential oil and different constituents of C. deodara as botanical larvicides for their use in pest management

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Analysis of Mice Lacking DNaseI Hypersensitive Sites at the 5′ End of the IgH Locus

The 5′ end of the IgH locus contains a cluster of DNaseI hypersensitive sites, one of which (HS1) was shown to be pro-B cell specific and to contain binding sites for the transcription factors PU.1, E2A, and Pax5. These data as well as the location of the hypersensitive sites at the 5′ border of the IgH locus suggested a possible regulatory function for these elements with respect to the IgH locus. To test this notion, we generated mice carrying targeted deletions of either the pro-B cell specific site HS1 or the whole cluster of DNaseI hypersensitive sites. Lymphocytes carrying these deletions appear to undergo normal development, and mutant B cells do not exhibit any obvious defects in V(D)J recombination, allelic exclusion, or class switch recombination. We conclude that deletion of these DNaseI hypersensitive sites does not have an obvious impact on the IgH locus or B cell development

Reading Scepticism Historically. Scepticism, Acatalepsia and the Fall of Adam in Francis Bacon

The first part of this paper will provide a reconstruction of Francis Bacon’s interpretation of Academic scepticism, Pyrrhonism, and Dogmatism, and its sources throughout his large corpus. It shall also analyze Bacon’s approach against the background of his intellectual milieu, looking particularly at Renaissance readings of scepticism as developed by Guillaume Salluste du Bartas, Pierre de la Primaudaye, Fulke Greville, and John Davies. It shall show that although Bacon made more references to Academic than to Pyrrhonian Scepticism, like most of his contemporaries, he often misrepresented and mixed the doctrinal components of both currents. The second part of the paper shall offer a complete chronological survey of Bacon’s assessment of scepticism throughout his writings. Following the lead of previous studies by other scholars, I shall support the view that, while he approved of the state of doubt and the suspension of judgment as a provisional necessary stage in the pursuit of knowledge, he rejected the notion of acatalepsia. To this received reading, I shall add the suggestion that Bacon’s criticism of acatalepsia ultimately depends on his view of the historical conditions that surround human nature. I deal with this last point in the third part of the paper, where I shall argue that Bacon’s evaluation of scepticism relied on his adoption of a Protestant and Augustinian view of human nature that informed his overall interpretation of the history of humanity and nature, including the sceptical schools

Intestinal ischemia after cardiac surgery: analysis of a large registry.

Intestinal ischemia after cardiac surgery is a rare but severe complication with a high mortality. Early surgery can be lifesaving. The aim was to analyze the incidence, outcome, and risk factors for these patients

Spacetimes for λ-deformations

We examine a recently proposed class of integrable deformations to two-dimensional conformal field theories. These {\lambda}-deformations interpolate between a WZW model and the non-Abelian T-dual of a Principal Chiral Model on a group G or, between a G/H gauged WZW model and the non-Abelian T-dual of the geometric coset G/H. {\lambda}-deformations have been conjectured to represent quantum group q-deformations for the case where the deformation parameter is a root of unity. In this work we show how such deformations can be given an embedding as full string backgrounds whose target spaces satisfy the equations of type-II supergravity. One illustrative example is a deformation of the Sl(2,R)/U(1) black-hole CFT. A further example interpolates between the SU(2)×SU(2)SU(2)×SL(2,R)×SL(2,R)SL(2,R)×U(1)4 gauged WZW model and the non-Abelian T-dual of AdS3×S3×T4 supported with Ramond flux