Eight Weeks of a High Dose of Curcumin Supplementation May Attenuate Performance Decrements Following Muscle-Damaging Exercise

Background: It is known that unaccustomed exercise—especially when it has an eccentric component—causes muscle damage and subsequent performance decrements. Attenuating muscle damage may improve performance and recovery, allowing for improved training quality and adaptations. Therefore, the current study sought to examine the effect of two doses of curcumin supplementation on performance decrements following downhill running. Methods: Sixty-three physically active men and women (21 ± 2 y; 70.0 ± 13.7 kg; 169.3 ± 15.2 cm; 25.6 ± 14.3 body mass index (BMI), 32 women, 31 men) were randomly assigned to ingest 250 mg of CurcuWIN® (50 mg of curcuminoids), 1000 mg of CurcuWIN® (200 mg of curcuminoids), or a corn starch placebo (PLA) for eight weeks in a double-blind, randomized, placebo-controlled parallel design. At the end of the supplementation period, subjects completed a downhill running protocol intended to induce muscle damage. Muscle function using isokinetic dynamometry and perceived soreness was assessed prior to and at 1 h, 24 h, 48 h, and 72 h post-downhill run. Results: Isokinetic peak extension torque did not change in the 200-mg dose, while significant reductions occurred in the PLA and 50-mg groups through the first 24 h of recovery. Isokinetic peak flexion torque and power both decreased in the 50-mg group, while no change was observed in the PLA or 200-mg groups. All the groups experienced no changes in isokinetic extension power and isometric average peak torque. Soreness was significantly increased in all the groups compared to the baseline. Non-significant improvements in total soreness were observed for the 200-mg group, but these changes failed to reach statistical significance. Conclusion: When compared to changes observed against PLA, a 200-mg dose of curcumin attenuated reductions in some but not all observed changes in performance and soreness after completion of a downhill running bout. Additionally, a 50-mg dose appears to offer no advantage to changes observed in the PLA and 200-mg groups

A temporal study of oxygen-rich pulsating variable AGB star, T Cep: Investigation on dust formation and dust properties

Pulsation is believed to be the leading cause of dusty mass loss from Asymptotic Giant Branch (AGB) stars. We present a temporal study of T Cep, a long-period Mira variable, using seven ISO SWS spectra, covering a 16-month period over a single pulsation cycle. The observed spectral dust features change over the pulsation cycle of this Mira. In general, the overall apparent changes in spectral features can be attributed to changes in the dust temperature, resulting from the intrinsic pulsation cycle of the central star. However, not all feature changes are so easily explained. Based on direct comparison with laboratory spectra of several potential minerals, the dust is best explained by crystalline iron-rich silicates. These findings contradict the currently favored dust formation hypotheses.Comment: This article has been accepted for publication in The Astrophysical Journal. It is tentatively scheduled for the May 10, 2011, v732 -2 issu

Evolution of Diffusion-Weighted Magnetic Resonance Imaging Signal Abnormality in Sporadic Creutzfeldt-Jakob Disease, With Histopathological Correlation

IMPORTANCE: Prion diseases represent the archetype of brain diseases caused by protein misfolding, with the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion-weighted imaging (DWI) has emerged as the most sensitive magnetic resonance imaging (MRI) sequence for the diagnosis of sCJD, but few studies have assessed the evolution of MRI signal as the disease progresses. OBJECTIVES: To assess the natural history of the MRI signal abnormalities on DWI in sCJD to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation. DESIGN, SETTING, AND PARTICIPANTS: Gray matter involvement on DWI was assessed among 37 patients with sCJD in 26 cortical and 5 subcortical subdivisions per hemisphere using a semiquantitative scoring system of 0 to 2 at baseline and follow-up. A total brain score was calculated as the summed scores in the individual regions. In 7 patients, serial mean diffusivity measurements were obtained. Age at baseline MRI, disease duration, atrophy, codon 129 methionine valine polymorphism, Medical Research Council Rating Scale score, and histopathological findings were documented. The study setting was the National Prion Clinic, London, England. All participants had a probable or definite diagnosis of sCJD and had at least 2 MRI studies performed during the course of their illness. The study dates were October 1, 2008 to April 1, 2012. The dates of our analysis were January 19 to April 20, 2012. MAIN OUTCOMES AND MEASURES: Correlation of regional and total brain scores with disease duration. RESULTS: Among the 37 patients with sCJD in this study there was a significant increase in the number of regions demonstrating signal abnormality during the study period, with 59 of 62 regions showing increased signal intensity (SI) at follow-up, most substantially in the caudate and putamen (P < .001 for both). The increase in the mean (SD) total brain score from 30.2 (17.3) at baseline to 40.5 (20.6) at follow-up (P = .001) correlated with disease duration (r = 0.47, P = .003 at baseline and r = 0.35, P = .03 at follow-up), and the left frontal SI correlated with the degree of spongiosis (r = 0.64, P = .047). Decreased mean diffusivity in the left caudate at follow-up was seen (P < .001). Eight patients demonstrated decreased SI in cortical regions, including the left inferior temporal gyrus and the right lingual gyrus. CONCLUSIONS AND RELEVANCE: Magnetic resonance images in sCJD show increased extent and degree of SI on DWI that correlates with disease duration and the degree of spongiosis. Although cortical SI may fluctuate, increased basal ganglia SI is a consistent finding and is due to restricted diffusion. Diffusion-weighted imaging in the basal ganglia may provide a noninvasive biomarker in future therapeutic trials

Discovery of Isotopes of the Transuranium Elements with 93 <= Z <= 98

One hundred and five isotopes of the transuranium elements neptunium, plutonium, americium, curium, berkelium and californium have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.Comment: To be published in Atomic Data and Nuclear Data Table

Transient dust in warm debris disks - Detection of Fe-rich olivine grains

(Abridged) Debris disks trace remnant reservoirs of leftover planetesimals in planetary systems. A handful of "warm" debris disks have been discovered in the last years, where emission in excess starts in the mid-infrared. An interesting subset within these warm debris disks are those where emission features are detected in mid-IR spectra, which points towards the presence of warm micron-sized dust grains. Given the ages of the host stars, the presence of these grains is puzzling, and questions their origin and survival in time. This study focuses on determining the mineralogy of the dust around 7 debris disks with evidence for warm dust, based on Spitzer/IRS spectroscopic data, in order to provide new insights into the origin of the dust grains. We present a new radiative transfer code dedicated to SED modeling of optically thin disks. We make use of this code on the SEDs of seven warm debris disks, in combination with recent laboratory experiments on dust optical properties. We find that most, if not all, debris disks in our sample are experiencing a transient phase, suggesting a production of small dust grains on relatively short timescales. From a mineralogical point of view, we find that enstatite grains have small abundances compared to crystalline olivine grains. The main result of our study is that we find evidences for Fe-rich crystalline olivine grains (Fe / [Mg + Fe] ~ 0.2) for several debris disks. This finding contrasts with studies of gas-rich protoplanetary disks. The presence of Fe-rich olivine grains, and the overall differences between the mineralogy of dust in Class II disks compared to debris disks suggest that the transient crystalline dust is of a new generation. We discuss possible crystallization routes to explain our results, and comment on the mechanisms that may be responsible for the production of small dust grains

Inhibition of KCa2.2 and KCa2.3 channel currents by protonation of outer pore histidine residues

Ion channels are often modulated by changes in extracellular pH, with most examples resulting from shifts in the ionization state of histidine residue(s) in the channel pore. The application of acidic extracellular solution inhibited expressed KCa2.2 (SK2) and KCa2.3 (SK3) channel currents, with KCa2.3 (pIC50 of ∼6.8) being approximately fourfold more sensitive than KCa2.2 (pIC50 of ∼6.2). Inhibition was found to be voltage dependent, resulting from a shift in the affinity for the rectifying intracellular divalent cation(s) at the inner mouth of the selectivity filter. The inhibition by extracellular protons resulted from a reduction in the single-channel conductance, without significant changes in open-state kinetics or open probability. KCa2.2 and KCa2.3 subunits both possess a histidine residue in their outer pore region between the transmembrane S5 segment and the pore helix, with KCa2.3 also exhibiting an additional histidine residue between the selectivity filter and S6. Mutagenesis revealed that the outer pore histidine common to both channels was critical for inhibition. The greater sensitivity of KCa2.3 currents to protons arose from the additional histidine residue in the pore, which was more proximal to the conduction pathway and in the electrostatic vicinity of the ion conduction pathway. The decrease of channel conductance by extracellular protons was mimicked by mutation of the outer pore histidine in KCa2.2 to an asparagine residue. These data suggest that local interactions involving the outer turret histidine residues are crucial to enable high conductance openings, with protonation inhibiting current by changing pore shape

Solo status and women's spatial test performance: the role of individuation tendencies

The impact of anticipated solo status on women's spatial performance was investigated in an experimental study. The study was designed to test whether the underperformance of women entering testing situations who find themselves to be the only woman present is related to a tendency to individuate the self. Women performed a test of spatial ability under conditions of anticipated solo or non-solo status and responded to a measure of self-construal. In line with previous research, we found a disrupting solo status effect on women's performance on the spatial ability test. Most importantly, the negative effect of solo status on performance was partially mediated by individuation tendencies as reflected in a decreased predominance of the interdependent (as compared to the independent) level of the self under solo status conditions. These findings indicate that individuation tendencies play a crucial role in the process triggered in test takers under threatening performance situations. Copyright © 2007 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60972/1/490_ftp.pd

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit

Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress-gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-of-hypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis