I See! Scotland: Tackling sectarianism and promoting community psychosocial health

We developed and tested through two studies a new intervention run as a course, I SEE! Scotland, to reduce and prevent Protestant-Catholic sectarianism in Scotland, a historic inter-group conflict expressed in forms ranging from polite to violent, within a wider population that includes those who feel untouched. Designed to reflect the social ecology of Scotland and engage individuals regardless of sectarian involvement, the intervention aimed to increase cognitive complexity, measured as integrative complexity, through participatory theatre and experiential methods. We hypothesised that the confluence of experiential learning to support multiple forms of self, other, and systems awareness with narrative framing would increase integrative complexity management capacities. Tested with a diverse sample of 104 participants (secondary school staff; achieving, disruptive or vulnerable students; young adults returning to education; other professionals; prisoners; recovering drug addicts; unemployed), study one pre-post comparisons showed significant integrative complexity gains that cohered with second end of intervention integrative complexity measures, replicating results from other integrative complexity interventions despite differences in samples, conflicts, and context. Study two with twenty-eight of the one hundred and four participants showed significant pre post increases in resilience. These results predict peaceful outcomes to intergroup conflict, tackling sectarianism and promoting community psychosocial health. We note future research plans

Assessment of two screening tools to identify psoriatic arthritis in patients with psoriasis

Background: Many patients with psoriasis have undiagnosed psoriatic arthritis. Low specificity is found with many PsA screening tools. A new instrument, the CONTEST questionnaire, was developed utilizing the most discriminative items from existing instruments. Objective: The aim of this study was to compare the CONTEST and PEST screening tools. Methods: People attending secondary care clinics with psoriasis, but not PsA, completed the questionnaires, were assessed for function and quality of life, and had a physical examination. Patients thought to have PsA were compared to those without. The performance of CONTEST and PEST was compared using area under the receiver operating curve (AUC), and sensitivity and specificity at the previously published cut‐offs. Results: A total of 451 dermatology patients were approached, 35% were reviewed and 27 (17%, 95% CI 12.3–21.7) had unidentified psoriatic arthritis. The sensitivity and specificity (95% CI) of PEST were 0.60 (0.42–0.78)/0.76 (0.69–0.83) and for CONTEST 0.53 (0.34–0.72)/0.71 (0.63–0.79). The confidence limits for the AUC overlapped (AUC for PEST 0.72 (0.61–0.84), for CONTEST 0.66 (0.54–0.77). Conclusions: PEST and CONTEST questionnaires performed equally well, with no superiority of the new CONTEST tool

Is no news good news? Inconclusive genetic test results in BRCA1 and BRCA2 from patients and professionals' perspectives

<p>Abstract</p> <p>Background</p> <p>Women from families with a high risk of breast or ovarian cancer in which genetic testing for mutations in the <it>BRCA1/2 </it>genes is inconclusive are a vulnerable and understudied group. Furthermore, there are no studies of the professional specialists who treat them - geneticists, genetic counsellors/nurses, oncologists, gynaecologists and breast surgeons.</p> <p>Methods</p> <p>We conducted a small qualitative study that investigated women who had developed breast cancer under the age of 45 and who had an inconclusive <it>BRCA1/2 </it>genetic diagnostic test (where no mutations or unclassified variants were identified). We arranged three focus groups for affected women and their close female relatives - 13 women took part. We also interviewed 12 health professionals who were involved in the care of these women.</p> <p>Results</p> <p>The majority of the women had a good grasp of the meaning of their own or a family member's inconclusive result, but a few indicated some misunderstanding. Most of the women in this study underwent the test for the benefit of others in the family and none mentioned that they were having the test purely for themselves. A difficult issue for sisters of affected women was whether or not to undertake prophylactic breast surgery. The professionals were sensitive to the difficulties in explaining an inconclusive result. Some felt frustrated that technology had not as yet provided them with a better tool for prediction of risk.</p> <p>Conclusions</p> <p>Some of the women were left with the dilemma of what decision to make regarding medical management of their cancer risk. For the most part, the professionals believed that the women should be supported in whatever management decisions they considered best, provided these decisions were based on a complete and accurate understanding of the genetic test that had taken place in the family.</p

Circulating CD14brightCD16+ 'intermediate' monocytes exhibit enhanced parasite pattern recognition in human helminth infection.

Circulating monocyte sub-sets have recently emerged as mediators of divergent immune functions during infectious disease but their role in helminth infection has not been investigated. In this study we evaluated whether 'classical' (CD14brightCD16-), 'intermediate' (CD14brightCD16+), and 'non-classical' (CD14dimCD16+) monocyte sub-sets from peripheral blood mononuclear cells varied in both abundance and ability to bind antigenic material amongst individuals living in a region of Northern Senegal which is co-endemic for Schistosoma mansoni and S. haematobium. Monocyte recognition of excretory/secretory (E/S) products released by skin-invasive cercariae, or eggs, of S. mansoni was assessed by flow cytometry and compared between S. mansoni mono-infected, S. mansoni and S. haematobium co-infected, and uninfected participants. Each of the three monocyte sub-sets in the different infection groups bound schistosome E/S material. However, 'intermediate' CD14brightCD16+ monocytes had a significantly enhanced ability to bind cercarial and egg E/S. Moreover, this elevation of ligand binding was particularly evident in co-infected participants. This is the first demonstration of modulated parasite pattern recognition in CD14brightCD16+ intermediate monocytes during helminth infection, which may have functional consequences for the ability of infected individuals to respond immunologically to infection

The immunopathology of ANCA-associated vasculitis.

The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Characterisation of side-chain conformational preferences in a biologically active but unfolded protein.

A combination of experimental NMR 3J alpha beta coupling constant measurements and theoretical predictions from a statistical model for a random coil have been used to characterise the conformations of amino acid side-chains in an unfolded fibronectin binding protein. The statistical model uses the distribution of torsion angles in a data base of native folded protein structures to provide a description of the torsion angle populations of each residue in a random coil. For all but three of the residues studied a close agreement is observed between the experimental 3J alpha beta data and the model predictions (correlation coefficient 0.90; RMSD 0.70 Hz). In these cases the populations about the chi 1 torsion angles in the conformational ensemble defining the fibronectin binding protein are well described by those present in the protein data base. For Phe 69, Asp 92 and Asp 105 however significant deviations are observed between the predictions and experimental data. Each of these side-chains is found to be involved in persistent non-random structural features arising from clustering of hydrophobic groups or interactions between charged side-chains. The analysis demonstrates the detailed insight that can be provided into conformationally disordered states by combining experimental and theoretical approaches

Insulin directly stimulates VEGF-A production in the glomerular podocyte

Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the podocyte in both mice and humans via the insulin receptor (IR). Insulin directly increased VEGF-A mRNA levels and protein production in conditionally immortalized wild-type human and murine podocytes. Furthermore, when podocytes were rendered insulin resistant in vitro (using stable short hairpin RNA knockdown of the IR) or in vivo (using transgenic podocyte-specific IR knockout mice), podocyte VEGF-A production was impaired. Importantly, in vivo, this occurs before the development of any podocyte damage due to podocyte insulin resistance. Modulation of VEGF-A by insulin in the podocyte may be another important factor in the development of glomerular disease associated with conditions in which insulin signaling to the podocyte is deranged. © 2013 the American Physiological Society.link_to_subscribed_fulltex