Cholecalciferol supplementation and angiogenic markers in chronic kidney disease

Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3-4. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and 13.40±4.42 ng/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to 27.06; p<0.001). Serum levels of angiogenic markers were similar at baseline. At 16 weeks, angiopoietin-2 level decreased in cholecalciferol group (mean difference:-0.73 ng/ml, 95%CI, -1.25 to -0.20, p = 0.002) but not in placebo group (mean difference -0.46 ng/ml, 95%CI, -1.09 to 0.17, p = 0.154), however there was no between-group difference at 16 weeks (between-group difference in mean change: -0.27 ng/ml, 95%CI, -1.09 to 0.55, p = 0.624). Serum angiopoietin-1 level increased [mean change: 5.63 (0.51 to 10.75), p = 0.018] and VEGF-R level decreased [mean change: -87.16 (-131.89 to -42.44), p<0.001] in placebo group but did not show any change in cholecalciferol group. Our data shows the changes in Ang-1, Ang-2 and Ang-1/Ang-2 ratio after high dose oral cholecalciferol supplementation in patients with non-diabetic G3-4 CKD. The data suggests changes in circulating levels of angiogenic markers which needs to be confirmed through an adequately powered study

Potential dose distributions at proposed surface radioactvity clearance levels resulting from occupational scenarios.

The purpose of this report is to evaluate the potential dose distribution resulting from surface radioactivity, using occupational radiation exposure scenarios. The surface radioactivity clearance values considered in this analysis may ultimately replace those currently specified in the U.S. Department of Energy (DOE) requirements and guidance for radiological protection of workers, the public and the environment. The surface contamination values apply to radioactive contamination deposited on a surface (i.e., not incorporated into the interior of the material). For these calculations, the dose coefficients for intake of radionuclides were taken from ICRP Publication 68 (ICRP 1994), and external exposure dose coefficients were taken from the compact disc (CD) that accompanied Federal Guidance Report (FGR) 13 (Eckerman et al. 1999). The ICRP Publication 68 dose coefficients were based on ICRP Publication 60 (ICRP 1990) and were used specifically for worker dose calculations. The calculated dose in this analysis is the 'effective dose' (ED), rather than the 'effective dose equivalent' (EDE)

The effects of paranoia and dopamine on perception of cohesion and conspiracy: a pre-registered, double-blind, placebo-controlled experiment

Paranoia is a common symptom of psychotic disorders but is also present on a spectrum of severity in the general population. Although paranoia is associated with an increased tendency to perceive cohesion and conspiracy within groups, the mechanistic basis of this variation remains unclear. One potential avenue involves the brain’s dopaminergic system, which is known to be altered in psychosis. In this study, we used large-N online samples to establish the association between trait paranoia and perceptions of cohesion and conspiracy. We further evaluated the role of dopamine on perceptions of cohesion and conspiracy using a double-blind, placebo-controlled laboratory experiment where participants received levodopa or a placebo control. Our results were mixed: group perceptions and perceptions of cohesion were higher among more paranoid individuals but were not altered under dopamine administration. We outline the potential reasons for these discrepancies and the broader implications for understanding paranoia in terms of dopamine dysregulation

Estimating risk of C. difficile transmission from PCR positive but cytotoxin negative cases

Background: The use of molecular methods to diagnose Clostridium difficile infection (CDI) has improved diagnostic yield compared to conventional methods. However, PCR testing can detect colonization and has introduced several practical challenges pertaining to need for treatment and isolation of cases. Methods: For all new cases detected by real-time PCR, concurrent cytotoxin assay was performed and genetic characterization with MLVA (multi-locus variable number tandem repeat analysis) was done to determine relatedness. We used PCR cycle threshold (Ct) of detection as surrogate marker for bacterial burden in stool. Results: Overall, 54 cases of CDI were detected during the study period. 42 were concurrently tested by CYT and characterized by MLVA. MLVA analysis revealed marked genetic diversity with no ongoing outbreaks; four cases were due to NAP1 strain. CYT-/PCR + cases had a higher median Ct value of detection compared to CYT+/PCR + cases (28.2 vs 22.5; p = 0.01). Among 25 strains that were genetically related, 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.02). Conclusion: CYT-/PCR+ cases contribute to hospital based transmission. However, the risk of transmission of C. difficile from CYT +/PCR+ cases may be higher than those that are CYT-/PCR+. © 2014 Kamboj et al

Flow-cytometric Analysis of Bacillus anthracis Spores

Flow-cytometric technique has been established as a powerful tool for detection andidentification of microbiological agents. Unambiguous and rapid detection of Bacillus anthracisspores has been reported using immunoglobulin G-fluorescein isothiocyanate conjugate againstlive spores. In addition to the high sensitivity, the present technique could differentiate betweenspores of closely related species, eg, Bacillus cereus and Bacillus subtilis using fluorescenceintensity. The technique can be used for detection of live as well as inactivated spores makingit more congenial for screening of suspected samples of bioterrorism

Activity-Dependent Modulation of Synaptic AMPA Receptor Accumulation

AbstractBoth theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured spinal neurons leads to an increase in mEPSC amplitudes, accompanied by an equivalent increase in the accumulation of AMPA receptors at synapses. Conversely, increasing excitatory synaptic activity leads to a decrease in synaptic AMPA receptors and a decline in mEPSC amplitude. The time course of this synaptic remodeling is slow, similar to the metabolic half-life of neuronal AMPA receptors. Moreover, inhibiting excitatory synaptic transmission significantly prolongs the half-life of the AMPA receptor subunit GluR1, suggesting that synaptic activity modulates the size of the mEPSC by regulating the turnover of postsynaptic AMPA receptors

Compassionate faces: Evidence for distinctive facial expressions associated with specific prosocial motivations

Compassion is a complex cognitive, emotional and behavioural process that has important real-world consequences for the self and others. Considering this, it is important to understand how compassion is communicated. The current research investigated the expression and perception of compassion via the face. We generated exemplar images of two compassionate facial expressions induced from two mental imagery tasks with different compassionate motivations (Study 1). Our kind- and empathic compassion faces were perceived differently and the empathic-compassion expression was perceived as best depicting the general definition of compassion (Study 2). Our two composite faces differed in their perceived happiness, kindness, sadness, fear and concern, which speak to their underling motivation and emotional resonance. Finally, both faces were accurately discriminated when presented along a compassion continuum (Study 3). Our results demonstrate two perceptually and functionally distinct facial expressions of compassion, with potentially different consequences for the suffering of others.CRB, PG, JAK and CJF were supported (MR/J009210/1) by the UK Medical Research Council (https://mrc.ukri.org/). JSL was supported by a grant (PP00P1_163758/1) from the Swiss National Science Foundation (www.snf.ch). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Contactless graphene conductivity mapping on a wide range of substrates with terahertz time-domain reflection spectroscopy.

We demonstrate how terahertz time-domain spectroscopy (THz-TDS) operating in reflection geometry can be used for quantitative conductivity mapping of large area chemical vapour deposited graphene films on sapphire, silicon dioxide/silicon and germanium. We validate the technique against measurements performed with previously established conventional transmission based THz-TDS and are able to resolve conductivity changes in response to induced back-gate voltages. Compared to the transmission geometry, measurement in reflection mode requires careful alignment and complex analysis, but circumvents the need of a terahertz transparent substrate, potentially enabling fast, contactless, in-line characterisation of graphene films on non-insulating substrates such as germanium.H.L. and J.A.Z. acknowledge financial support from the EPSRC (Grant No. EP/L019922/1). P.B.W. acknowledges EPSRC Cambridge NanoDTC EP/G037221/1. R.D., H.E.B. and D. R. acknowledge financial support from the EPSRC (Grant No. EP/J017671/1, Coherent Terahertz Systems). S.H. acknowledges funding from the EPSRC (Grant No. EP/K016636/1, GRAPHTED)

Ultra-thin plasmonic detectors

Plasmonic materials, and their ability to enable strong concentration of optical fields, have offered a tantalizing foun- dation for the demonstration of sub-diffraction-limit photonic devices. However, practical and scalable plasmonic optoelectronics for real world applications remain elusive. In this work, we present an infrared photodetector leverag- ing a device architecture consisting of a “designer” epitaxial plasmonic metal integrated with a quantum-engineered detector structure, all in a mature III-V semiconductor material system. Incident light is coupled into surface plasmon- polariton modes at the detector/designer metal interface, and the strong confinement of these modes allows for a sub-diffractive (∼λ0/33) detector absorber layer thickness, effectively decoupling the detector’s absorption efficiency and dark current. We demonstrate high-performance detectors operating at non-cryogenic temperatures (T= 195 K), without sacrificing external quantum efficiency, and superior to well-established and commercially available detectors. This work provides a practical and scalable plasmonic optoelectronic device architecture with real world mid-infrared applications.Lockheed Martin; National Science Foundation (NNCI- 1542159); Defense Advanced Research Projects Agency (NASCENT, NLM program); Division of Materials Research (1720595); Division of Electrical, Communications and Cyber Systems (1926187).Center for Dynamics and Control of Material