Double-blind, randomised, placebo controlled, parallel group study of sativex® in the treatment of patients with peripheral neuropathic pain, associated with allodynia [poster]

No abstract available

Satisfaction, adherence and health-related quality of life with transdermal buprenorphine compared with oral opioid medications in the usual care of osteoarthritis pain

Background Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. Methods Patients in the UK with self-reported knee and/or hip OA who had been receiving one or more of TDB, co-codamol (an oral paracetamol/codeine combination) and tramadol for at least 1 month completed an online or telephone questionnaire. Medication satisfaction scores, HRQL scores (Short-Form 36 [SF-36]), medication adherence (Morisky Medication Adherence Scale [MMAS™]), adverse events and treatment discontinuations were recorded. Linear and logistic regression models were used to compare the treatment effect of TDB with co-codamol or tramadol. Results Overall, 966 patients met the inclusion criteria; 701 were taking only one of the target medications (TDB: 85; co-codamol: 373; tramadol: 243). The largest age group was 50–59 years and 76.0 % of patients were female. The TDB group was younger, with more male patients, therefore the statistical models were adjusted for age and sex. Medication satisfaction scores were significantly higher in the TDB group than the other two groups (TDB vs. co-codamol: 3.56, 95 % confidence interval [CI] 1.90–6.68, p < 0.0001; TDB vs. tramadol: 3.22, 95 % CI 1.67–6.20, p = 0.0005). Physical Component Summary scores for HRQL and mean adherence were also higher in the TDB group, while Mental Component Summary HRQL scores were similar across the three groups. Conclusions Patients with knee and/or hip OA pain treated with TDB were more satisfied and more adherent with their medication, and reported higher Physical Component Summary HRQL scores than those treated with co-codamol or tramadol, although demographic differences were observed between groups

Linking changes in pain severity to changes in other outcomes in patients with posttraumatic peripheral neuropathic pain treated with pregabalin [POSTER]

No abstract available

Structure dependent effects of Amyloid-β on long-term memory in Lymnaea stagnalis

Amyloid-β (Aβ) peptides are implicated in the causation of memory loss, neuronal impairment, and neurodegeneration in Alzheimer's disease. Our recent work revealed that Aβ 1–42 and Aβ 25–35 inhibit long-term memory (LTM) recall in Lymnaea stagnalis (pond snail) in the absence of cell death. Here, we report the characterization of the active species prepared under different conditions, describe which Aβ species is present in brain tissue during the behavioral recall time point and relate the sequence and structure of the oligomeric species to the resulting neuronal properties and effect on LTM. Our results suggest that oligomers are the key toxic Aβ1–42 structures, which likely affect LTM through synaptic plasticity pathways, and that Aβ 1–42 and Aβ 25–35 cannot be used as interchangeable peptides

Amyloidogenicity and toxicity of the reverse and scrambled variants of amyloid-β 1-42

β-amyloid 1-42 (Aβ1-42) is a self-assembling peptide that goes through many conformational and morphological changes before forming the fibrils that are deposited in extracellular plaques characteristic of Alzheimer's disease. The link between Aβ1-42 structure and toxicity is of major interest, in particular, the neurotoxic potential of oligomeric species. Many studies utilise reversed (Aβ42-1) and scrambled (AβS) forms of amyloid-β as control peptides. Here, using circular dichroism, thioflavin T fluorescence and transmission electron microscopy, we reveal that both control peptides self-assemble to form fibres within 24 h. However, oligomeric Aβ reduces cell survival of hippocampal neurons, while Aβ42-1 and Aβs have reduced effect on cellular health, which may arise from their ability to assemble rapidly to form protofibrils and fibrils

Kinetically controlled coassembly of multichromophoric peptide hydrogelators and the impacts on energy transport

We report a peptide-based multichromophoric hydrogelator system, wherein π-electron units with different inherent spectral energies are spatially controlled within peptidic 1-D nanostructures to create localized energy gradients in aqueous environments. This is accomplished by mixing different π-conjugated peptides prior to initiating self-assembly through solution acidification. We can vary the kinetics of the assembly and the degree of self-sorting through the choice of the assembly trigger, which changes the kinetics of acidification. The hydrolysis of glucono-δ-lactone (GdL) provides a slow pH drop that allows for stepwise triggering of peptide components into essentially self-sorted nanostructures based on subtle pKa differences, whereas HCl addition leads to a rapid formation of mixed components within a nanostructure. Using 1H NMR spectroscopy and fiber X-ray diffraction, we determine the conditions and peptide mixtures that favor self-sorting or intimate comixing. Photophysical investigations in the solution phase provide insight into the correlation of energy-transport processes occurring within the assemblies to the structural organization of the π-systems

Improving the estimation of deep-sea megabenthos biomass: dimension to wet weight conversions for abyssal invertebrates

Deep-sea megafaunal biomass has typically been assessed by sampling with benthic sledges and trawls, but non-destructive methods, particularly photography, are becoming increasingly common. Estimation of individual wet weight in seabed photographs has been achieved using equations obtained from measured trawl-caught specimens for a limited number of taxa. However, a lack of appropriate conversion factors has limited estimation across taxa encompassing whole communities. Here we compile relationships between measured body dimensions and preserved wet weights for a comprehensive catalogue of abyssal epibenthic megafauna, using ~47,000 specimens from the Porcupine Abyssal Plain (NE Atlantic) housed in the Discovery Collections. The practical application of the method is demonstrated using an extremely large dataset of specimen measurements from seabed photographs taken in the same location. We also collate corresponding field data on fresh wet weight, to estimate the impact of fixation in formalin and preservation in industrial denatured alcohol on the apparent biomass. Taxa with substantial proportions of soft tissues lose 35 to 60% of their wet weight during preservation, while those with greater proportions of hard tissues lose 10 to 20%. Our total estimated fresh wet weight biomass of holothurians and cnidarians in the photographic survey was ~20 times the previous estimates of total invertebrate biomass based on trawl catches. This dramatic uplift in megabenthic biomass has significant implications for studies of standing stocks, community metabolism, and numerical modelling of benthic carbon flows

Causes and consequences of psychological distress among orphans in eastern Zimbabwe.

Substantial resources are invested in psychological support for children orphaned or otherwise made vulnerable in the context of HIV/AIDS (OVC). However, there is still only limited scientific evidence for greater psychological distress amongst orphans and even less evidence for the effectiveness of current support strategies. Furthermore, programmes that address established mechanisms through which orphanhood can lead to greater psychological distress should be more effective. We use quantitative and qualitative data from Eastern Zimbabwe to measure the effects of orphanhood on psychological distress and to test mechanisms for greater distress amongst orphans suggested in a recently published theoretical framework

Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils

Gaia on-board metrology: basic angle and best focus

The Gaia payload ensures maximum passive stability using a single material, SiC, for most of its elements. Dedicated metrology instruments are, however, required to carry out two functions: monitoring the basic angle and refocusing the telescope. Two interferometers fed by the same laser are used to measure the basic angle changes at the level of $\mu$as (prad, micropixel), which is the highest level ever achieved in space. Two Shack-Hartmann wavefront sensors, combined with an ad-hoc analysis of the scientific data are used to define and reach the overall best-focus. In this contribution, the systems, data analysis, procedures and performance achieved during commissioning are presentedComment: 18 pages, 14 figures. To appear in SPIE proceedings 9143-30. Space Telescopes and Instrumentation 2014: Optical, Infrared, and Millimeter Wav