Patient perspectives of managing fatigue in ankylosing spondylitis, and views on potential interventions: a qualitative study

<p>Background: Fatigue is a major component of living with ankylosing spondylitis (AS), though it has been largely over-looked, and currently there are no specific agreed management strategies.</p> <p>Methods: This qualitative exploratory study involved participants who are members of an existing population-based ankylosing spondylitis (PAS) cohort. Participants residing in South West Wales were invited to participate in a focus group to discuss; (1) effects of fatigue, (2) self-management strategies and (3) potential future interventions. The focus groups were audio-recorded and the transcripts were analysed using thematic analysis.</p> <p>Results: Participants consisted of 3 males/4 females (group 1) and 4 males/3 females (group 2), aged between 35 and 73 years (mean age 53 years). Three main themes were identified: (1) The effects of fatigue were multi-dimensional with participants expressing feelings of being ‘drained’ (physical), ‘upset’ (emotional) and experiencing ‘low-mood’ (psychological); (2) The most commonly reported self-management strategy for fatigue was a balanced combination of activity (exercise) and rest. Medication was reluctantly taken due to side-effects and worries over dependency; (3) Participants expressed a preference for psychological therapies rather than pharmacological for managing fatigue. Information on Mindfulness-Based Stress Reduction (MBSR) was received with interest, with recommendations for delivery in a group format with the option of distance-based delivery for people who were not able to attend a group course.</p> <p>Conclusions: Patients frequently try and manage their fatigue without any formal guidance or support. Our research indicates there is a need for future research to focus on psychological interventions to address the multi-faceted aspects of fatigue in AS.</p&gt

An easy-to-machine electrochemical flow microreactor: efficient synthesis of isoindolinone and flow functionalization

Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow proces

Self-assembly of telechelic tyrosine end-capped PEO and poly(alanine) polymers in aqueous solution

The self-assembly in aqueous solution of three novel telechelic conjugates comprising a central hydrophilic polymer and short (trimeric or pentameric) tyrosine end-caps has been investigated. Two of the conjugates have a central poly(oxyethylene) (polyethylene oxide, PEO) central block with different molar masses. The other conjugate has a central poly(l-alanine) (PAla) sequence in a purely amino-acid based conjugate. All three conjugates self-assemble into β-sheet based fibrillar structures, although the fibrillar morphology revealed by cryogenic-TEM is distinct for the three polymers—in particular the Tyr5-PEO6k-Tyr5 forms a population of short straight fibrils in contrast to the more diffuse fibril aggregates observed for Tyr5-PEO2k-Tyr5 and Tyr3-PAla-Tyr3. Hydrogel formation was not observed for these samples (in contrast to prior work on related systems) up to quite high concentrations, showing that it is possible to prepare solutions of peptide–polymer-peptide conjugates with hydrophobic end-caps without conformational constraints associated with hydrogelation. The Tyr5-PEO6k-Tyr5 shows significant PEO crystallization upon drying in contrast to the Tyr5-PEO2k-Tyr5 conjugate. Our findings point to the remarkable ability of short hydrophobic peptide end groups to modulate the self-assembly properties of polymers in solution in model peptide-capped “associative polymers”. Retention of fluidity at high conjugate concentration may be valuable in potential future applications of these conjugates as bioresponsive or biocompatible materials, for example exploiting the enzyme-responsiveness of the tyrosine end-group

QSAR rationales for the 1,2-diarylcyclopentenes as prostaglandin EP1 receptor antagonists: Potentially useful in the treatment of inflammatory pain

The EP1 receptor inhibitory activity of 1,2-diarylcyclopentene derivatives have been quantitatively analyzed in terms of Dragon descriptors. The derived QSAR models have provided rationales to explain the EP1 receptor inhibitory activity of 1,2-diarylcyclopentene derivatives. The 2D-autocorrelation descriptors (MATS4e, MATS5e, MATS7v, GATS5e and GATS7v) have highlighted the role of atomic properties in respective lags of autocorrelations to explain the biological actions of 1,2-diarylcyclopentene analogues. Presence of fluorine atom (nF) and smaller distance between N and O atoms (T(N..O)) in molecular structures, in addition to Kier-Hall electrotopological states (Ss) have also shown prevalence to optimize the EP1 receptor inhibitory activity. Partial least square analysis has confirmed the dominance of information content of the combinatorial protocol in multiple linear regression identified descriptors. Applicability domain analysis revealed that the suggested model matches the high quality parameters with good fitting power and capability of assessing external data. All the compounds are within the applicability domain of the proposed model and were evaluated correctly

Relations between self-reported daily-life fatigue, hearing status and pupil dilation during a speech perception in noise task

Objective: people with hearing impairment are likely to experience higher levels of fatigue due to effortful listening in daily communication. This hearing-related fatigue might not only constrain their work performance, but also result in withdrawal from major social roles. Therefore, it is important to understand the relationships between fatigue, listening effort, and hearing impairment, by examining the evidence from both subjective and objective measurements. The aim of the present study was to investigate these relationships by assessing subjectively measured daily-life fatigue (self-report questionnaires) and objectively measured listening effort (pupillometry) in both normally-hearing and hearing-impaired participants. Design: twenty-seven normally-hearing and 19 age-matched participants with hearing impairment were included in this study. Two self-report fatigue questionnaires: Need For Recovery and Checklist Individual Strength were given to the participants before the test session to evaluate the subjectively measured daily fatigue. Participants were asked to perform a speech reception threshold test with single-talker masker targeting a 50% correct response criterion. The pupil diameter was recorded during the speech processing, and we used peak pupil dilation as the main outcome measure of the pupillometry. Results: No correlation was found between subjectively measured fatigue and hearing acuity, nor was a group difference found between the normally-hearing and the hearing-impaired participants on the fatigue scores. A significant negative correlation was found between self-reported fatigue and peak pupil dilation. A similar correlation was also found between Speech Intelligibility Index required for 50% correct and peak pupil dilation. Multiple regression analysis showed that factors representing 'hearing acuity' and 'self-reported fatigue' had equal and independent associations with the peak pupil dilation during the speech in noise test. Less fatigue and better hearing acuity were associated with a larger pupil dilation. Conclusions: To the best of our knowledge, this is the first study to investigate the relationship between a subjective measure of daily-life fatigue and an objective measure of pupil dilation, as an indicator of listening effort. These findings help to provide an empirical link between pupil responses, as observed in the laboratory, and daily life fatigue

Computer-aided diagnosis of skeletal metastases in multi-parametric whole-body MRI

This work was funded by the Brussels Institute for Research and Innovation (Innoviris) -award number PFS-15. The resources and services used in this work were provided by the VSC (Flemish Supercomputer Center) , funded by the Research Foundation Flanders (FWO) and the Flemish Government

Chemical Ubiquitination for Decrypting a Cellular Code

The modification of proteins with ubiquitin (Ub) is an important regulator of eukaryotic biology and deleterious perturbation of this process is widely linked to the onset of various diseases. The regulatory capacity of the Ub signal is high and, in part, arises from the capability of Ub to be enzymatically polymerised to form polyubiquitin (polyUb) chains of eight different linkage types. These distinct polyUb topologies can then be site-specifically conjugated to substrate proteins to elicit a number of cellular outcomes. Therefore, to further elucidate the biological significance of substrate ubiquitination, methodologies that allow the production of defined polyUb species, and substrate proteins that are site-specifically modified with them, are essential to progress our understanding. Many chemically inspired methods have recently emerged which fulfil many of the criteria necessary for achieving deeper insight into Ub biology. With a view to providing immediate impact in traditional biology research labs, the aim of this review is to provide an overview of the techniques that are available for preparing Ub conjugates and polyUb chains with focus on approaches that use recombinant protein building blocks. These approaches either produce a native isopeptide, or analogue thereof, that can be hydrolysable or non-hydrolysable by deubiquitinases. The most significant biological insights that have already been garnered using such approaches will also be summarized

Modality redundancy for MRI-based glioblastoma segmentation

This study was funded by the EU-funded HosmartAI project(grant number 101016834)

Preparation of halomethaneboronates

A facile preparation of iodomethaneboronic esters is described. The key step utilizes a tin hydride reduction of dichloromethaneboronic esters.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23897/1/0000136.pd

Hydroformylation as a simple and efficient one carbon homologation of homoallylic alcohols. Synthesis of prelog-djerassi lactone.

A hydroformylation oxidation sequence is described for the efficient conversion of homoallylic alcohols to [delta]-lactones. The methodology is applied to the synthesis of Prelog-Djerassi lactone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25035/1/0000462.pd