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    Clinical and Experimental Dermatology 11/2013;
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    ABSTRACT: As a foundation for considering how gains may be maintained following early intervention in first-episode psychosis (FEP), this study aimed to describe and investigate factors predicting post-discharge relapse and longer term functioning. An evaluation via case-note review obtained quantitative data on 163 patients sequentially discharged from Birmingham Early Intervention Service (EIS) followed up for a median of 3.6 years. Time to relapse was calculated and hierarchical regression was used to determine predictors of relapse and functioning. Patients likely to relapse do so within the first year post-discharge; however, over 40% did not relapse during the follow-up period. The number of relapses occurring during EIS care predicted time-to-relapse post-discharge. At discharge from the EIS and study end-point, the proportion with low social and vocational functioning remained high. Predictors of positive 'Not in Education Employment or Training' status at end-point include being in a minority ethnic group, substance misuse and number of relapses. Increased emphasis on relapse prevention and early post-discharge monitoring may be needed, especially in the first year, for those who have experienced previous relapse. To maintain early outcomes in FEP, targeted interventions to address substance misuse and functional recovery need to be sustained in the long term. EISs should aim to make the first episode of psychosis the last. Services providing care for patients with psychosis post EIS should be designed to deliver care for ongoing need, with continued emphasis on relapse prevention and social recovery.
    Early Intervention in Psychiatry 11/2013;
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    ABSTRACT: US students with higher spirituality scores report better health and life satisfaction. This is the first UK study to explore the relationship between spirituality, health and life satisfaction of undergraduate students. Over 500 undergraduates completed an online questionnaire. Significant differences in spirituality score were present across college, ethnicity and religious belief. There appears to be a desire for spirituality amongst many students. Universities have a role to play in supporting students' search for meaning and purpose. Additional research is warranted to further understand the role of spirituality in the health and well-being of undergraduates.
    Journal of Religion and Health 11/2013;
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    ABSTRACT: In a previous study we found a very high prevalence of psychological distress in mothers of children admitted to a nutritional rehabilitation unit (NRU) in Malawi, Africa. The objective of this study was to compare the prevalence and severity of maternal distress within the NRU with that in other paediatric wards. Given the known association between poor maternal psychological well-being and child undernutrition in low- and middle-income countries, we hypothesised that distress would be higher among NRU mothers. Mothers of consecutive paediatric inpatients in a NRU, a high-dependency (and research) unit and an oncology ward were assessed for psychological distress using the Self-Reporting Questionnaire (SRQ). Two hundred sixty-eight mothers were interviewed (90.3% of eligible). The prevalence of SRQ score ≥8 was 35/150 {23.3% [95% confidence interval (CI) 16.8- 30.9%]} on the NRU, 13/84 [15.5% (95% CI 8.5-25.0%)] on the high-dependency unit and 7/34 [20.6% (95% CI 8.7-37.9%)] on the oncology ward (χ(2) = 2.04, P = 0.36). In linear regression analysis, the correlates of higher SRQ score were child diarrhoea on admission, child diagnosed with tuberculosis, and maternal experience of abuse by partner; child height-for-age z-score fell only just outside significance (P = 0.05). In summary, we found no evidence of greater maternal distress among the mothers of severely malnourished children within the NRU compared with mothers of paediatric inpatients with other severe illnesses. However, in support of previous research findings, we found some evidence that poor maternal psychological well-being is associated with child stunting and diarrhoea.
    Maternal and Child Nutrition 11/2013;
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    ABSTRACT: To assess the accuracy and reproducibility of biometry undertaken with the Aladdin (Topcon, Tokyo, Japan) in comparison with the current gold standard device, the IOLMaster 500 (Zeiss, Jena, Germany). University Eye Clinic, Birmingham, UK and Refractive Surgery Centre, Kiel, Germany. The right eye of 75 patients with cataracts and 22 healthy participants were assessed using the two devices. Measurements of axial length (AL), anterior chamber depth (ACD) and keratometry (K) were undertaken with the Aladdin and IOLMaster 500 in random order by an experienced practitioner. A second practitioner then obtained measurements for each participant using the Aladdin biometer in order to assess interobserver variability. No statistically significant differences (p>0.05) between the two biometers were found for average difference (AL)±95% CI=0.01±0.06 mm), ACD (0.00±0.11 mm) or mean K values (0.08±0.51 D). Furthermore, interobserver variability was very good for each parameter (weighted κ≥0.85). One patient's IOL powers could not be calculated with either biometer measurements, whereas a further three could not be analysed by the IOLMaster 500. The IOL power calculated from the valid measurements was not statistically significantly different between the biometers (p=0.842), with 91% of predictions within±0.25 D. The Aladdin is a quick, easy-to-use biometer that produces valid and reproducible results that are comparable with those obtained with the IOLMaster 500.
    The British journal of ophthalmology 11/2013;
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    ABSTRACT: Inhibitors targeting the hepatitis C virus (HCV) encoded viroporin, p7 prevent virus release in vitro. HCV can transmit by cell-free particle infection of new target cells and via cell-to-cell dependent contact with limited exposure to the extracellular environment. The role of assembly inhibitors in preventing HCV transmission via these pathways has not been studied. We compared the efficacy of three published p7 inhibitors to inhibit cell-free and cell-to-cell transmission of two chimeric HCV strains encoding genotype 2 (GT2) or 5 (GT5) p7 using a recently developed single cycle co-culture assay. The inhibitors reduced the infectivity of extracellular GT2 and GT5 virus by 80-90% and GT2 virus cell-to-cell transmission by 50%. However, all of the p7 inhibitors had minimal effect on GT5 cell-contact dependent transmission. Screening a wider panel of diverse viral genotypes demonstrated that p7 viroporin inhibitors were significantly more effective at blocking cell-free virus than cell-to-cell transmission. These results suggest an altered assembly or trafficking of cell-to-cell transmitted compared to secreted virus. These observations have important implications for the validation, therapeutic design and testing of HCV assembly inhibitors.
    Antiviral research 10/2013;
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    ABSTRACT: EBV elicits primary CD8(+) T cell responses that, by T cell cloning from infectious mononucleosis (IM) patients, appear skewed toward immediate early (IE) and some early (E) lytic cycle proteins, with late (L) proteins rarely targeted. However, L Ag-specific responses have been detected regularly in polyclonal T cell cultures from long-term virus carriers. To resolve this apparent difference between responses to primary and persistent infection, 13 long-term carriers were screened in ex vivo IFN-γ ELISPOT assays using peptides spanning the two IE, six representative E, and seven representative L proteins. This revealed memory CD8 responses to 44 new lytic cycle epitopes that straddle all three protein classes but, in terms of both frequency and size, maintain the IE > E > L hierarchy of immunodominance. Having identified the HLA restriction of 10 (including 7 L) new epitopes using memory CD8(+) T cell clones, we looked in HLA-matched IM patients and found such reactivities but typically at low levels, explaining why they had gone undetected in the original IM clonal screens. Wherever tested, all CD8(+) T cell clones against these novel lytic cycle epitopes recognized lytically infected cells naturally expressing their target Ag. Surprisingly, however, clones against the most frequently recognized L Ag, the BNRF1 tegument protein, also recognized latently infected, growth-transformed cells. We infer that BNRF1 is also a latent Ag that could be targeted in T cell therapy of EBV-driven B-lymphoproliferative disease.
    The Journal of Immunology 10/2013;
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    ABSTRACT: While the innate immune system has long been implicated in the pathogenesis of COPD, a role for the acquired immune system is less well studied. The increasing recognition that COPD shares features with autoimmune disease has led to interest in a potential role for regulatory T cells, which are intimately involved in the control of autoimmunity. The suggestion that regulatory T cell numbers are increased in patients with COPD may indicate their dysfunction or resistance to suppression by target cells. Investigation of regulatory T cells may therefore be of importance in understanding the inflammation and tissue damage that occurs in patients with COPD who cease smoking.
    Thorax 10/2013;
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    ABSTRACT: Introduction In 2012 a national, standardised approach was taken to UK Dental Foundation 1 recruitment. Prior to that recruitment method was at the discretion of individual Deaneries. The new national system is interactive, including simulated patients to see how applicants perform in a clinical communication context. A question was whether simulated patient scores could/should be awarded as well as clinicians' scores. This paper presents score data collected in the first round of national DF1 recruitment centres, with focus on how clinical examiners and trained simulated patients rated applicants.Method At the live recruitment events across four national centres score data were collected from observing clinical assessors and simulated patients on the communication station. On this occasion only the clinician awarded scores 'counted', but all simulated patients completed marking sheets to enable the process to be evaluated. Data were retrospectively analysed to test the hypotheses that there would be no significant scoring differences between centres and that inter-rater reliability, by applicant, between paired clinicians, and between clinicians and simulated patients would be strong.Results Results showed encouraging consistency between assessors, with some differences between centres. Clinicians were more likely to offer a borderline score. In communication analyses empathy had the weakest correlation with the overall score, while professional attitude had the strongest correlation. Data supported the hypothesis that trained simulated patients can be considered as assessors. Their future inclusion offers candidates a dual perspective (clinical and non-clinical) on performance, and saves clinical time.Discussion Simulated patients scored consistently and value can be added by including different perspectives in interactive assessment. Robust training is needed in all assessor training.Conclusion Simulated patients can usefully contribute to scoring in national dental recruitment centres. Lessons learned here can inform other dental assessments where stakeholders are already using, or considering using, simulated patients as assessors or co-assessors.
    British dental journal official journal of the British Dental Association: BDJ online 08/2013; 215(3):125-30.
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    ABSTRACT: This study determined the influence of physiologically relevant concentrations of C-reactive protein (CRP) on reactive oxygen species (ROS) production by neutrophils. Neutrophils from healthy individuals were incubated with soluble pentameric CRP prior to TLR stimulation with Fusobacterium nucleatum, or FcγR stimulation with IgG-opsonised Staphylococcus aureus or heat-aggregated IgG. ROS generation by unstimulated cells and those after stimulation were determined using luminol, isoluminol and lucigenin chemiluminescence, detecting predominantly intracellular hypochlorous acid (HOCl), extracellular hydrogen peroxide (detected as HOCl) and extracellular superoxide respectively. Baseline (unstimulated) neutrophil ROS generation and release was reduced compared with vehicle control by 10 µg/ml CRP. There was no consistent effect of CRP on FcγR-stimulated HOCl production, but the extracellular superoxide response was reduced by 10 µg/ml CRP. By contrast, CRP reduced intracellular (10 µg/ml) and extracellular (3 and 10 µg/ml) HOCl generation, but increased superoxide release (1-10 µg/ml) in response to TLR stimulation. Physiologically relevant concentrations of CRP inhibited baseline ROS generation and reduced FcγR-stimulated extracellular superoxide and TLR-stimulated HOCl release, suggesting that CRP may offer some degree of host protection from neutrophil-associated, low-level oxidative stress. However, CRP enhanced TLR-mediated superoxide release from neutrophils, potentially increasing oxidative stress but aiding host protection from infection.
    Innate Immunity 07/2013;
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