A myth-busting mental health tour of the National Gallery in London: Facilitators and challenges to its development and evaluation.

This paper describes a mental health-awareness audio tour of the National Gallery, London, and evaluates the development and implementation of the tour. This smartphone-based audio tour was co-produced by Gallery staff, young people with lived experience of mental health issues, academics, and technologists. Interviews (N = 22) were conducted with developers and data-collectors (who had gathered feedback from Gallery visitors who undertook the tour) with responses analysed thematically. Participants highlighted the value of the arts to raise awareness about mental health, and the importance of teamwork, lived experience, and co-production, but also raised the challenges of integrating low-budget projects into large-scale venues.

Impact on public attitudes of a mental health audio tour of the National Gallery in London.

AIM: The arts have the potential to increase public awareness about mental health and reduce stigma. However, arts-based projects to raise awareness have been small-scale. In this study, a mental health-awareness audio tour of The National Gallery in London was co-produced and narrated by young adults with relevant lived experience. The study investigated the acceptability of the tour to the public and evaluated its impact on public attitudes about mental health. METHODS: Participants were Gallery visitors over four consecutive days. The tour led visitors on 10 stops through the Gallery. Each stop focused on artworks and Gallery spaces, challenged common myths about mental health, and invited visitors to consider their personal views. Participants completed measures of mood and attitudes about mental health pre- and post-tour and provided narrative feedback. RESULTS: Pre-tour, participants (N = 213) reported high levels of happiness, compassion towards people with mental health conditions, comfort talking about mental health, and positive attitudes about mental health. Post-tour, participants (N = 111) reported significant increases in happiness, comfort, and positive attitudes. In feedback, participants (N = 85) reported that strengths of the tour were the music, inclusion of lived experience, art and mental health links, and reported that the tour was informative, innovative, and improved mental health awareness. CONCLUSIONS: The tour increased positive attitudes, despite positive baseline attitudes, indicating the feasibility of arts-based interventions in major venues to reduce stigma. Sampling limitations and participant retention suggest that arts-based projects to raise awareness should target more diverse audiences and consider data collection strategies in large venues.

Variation in the prion protein gene (PRNP) sequence of wild deer in Great Britain and mainland Europe.

Susceptibility to prion diseases is largely determined by the sequence of the prion protein gene (PRNP), which encodes the prion protein (PrP). The recent emergence of chronic wasting disease (CWD) in Europe has highlighted the need to investigate PRNP gene diversity in European deer species, to better predict their susceptibility to CWD. Here we report a large genetic survey of six British deer species, including red (Cervus elaphus), sika (Cervus nippon), roe (Capreolus capreolus), fallow (Dama dama), muntjac (Muntiacus reevesii), and Chinese water deer (Hydropotes inermis), which establishes PRNP haplotype and genotype frequencies. Two smaller data sets from red deer in Norway and the Czech Republic are also included for comparison. Overall red deer show the most PRNP variation, with non-synonymous/coding polymorphisms at codons 98, 168, 226 and 247, which vary markedly in frequency between different regions. Polymorphisms P168S and I247L were only found in Scottish and Czech populations, respectively. T98A was found in all populations except Norway and the south of England. Significant regional differences in genotype frequencies were observed within both British and European red deer populations. Other deer species showed less variation, particularly roe and fallow deer, in which identical PRNP gene sequences were found in all individuals analysed. Based on comparison with PRNP sequences of North American cervids affected by CWD and limited experimental challenge data, these results suggest that a high proportion of wild deer in Great Britain may be susceptible to CWD.

Animal prion diseases: the risks to human health.

Transmissible spongiform encephalopathies (TSEs) or prion diseases of animals notably include scrapie in small ruminants, chronic wasting disease (CWD) in cervids and classical bovine spongiform encephalopathy (C-BSE). As the transmission barrier phenomenon naturally limits the propagation of prions from one species to another, and the lack of epidemiological evidence for an association with human prion diseases, the zoonotic potential of these diseases was for a long time considered negligible. However, in 1996, C-BSE was recognized as the cause of a new human prion disease, variant Creutzfeldt-Jakob disease (vCJD), which triggered an unprecedented public health crisis in Europe. Large-scale epidemio-surveillance programs for scrapie and C-BSE that were implemented in the EU after the BSE crisis revealed that the distribution and prevalence of prion diseases in the ruminant population had previously been underestimated. They also led to the recognition of new forms of TSEs (named atypical) in cattle and small ruminants and to the recent identification of CWD in Europe. At this stage, the characterization of the strain diversity and zoonotic abilities associated with animal prion diseases remains largely incomplete. However, transmission experiments in nonhuman primates and transgenic mice expressing human PrP clearly indicate that classical scrapie, and certain forms of atypical BSE (L-BSE) or CWD may have the potential to infect humans. The remaining uncertainties about the origins and relationships between animal prion diseases emphasize the importance of the measures implemented to limit human exposure to these potentially zoonotic agents, and of continued surveillance for both animal and human prion diseases.

The zoonotic potential of animal prion diseases.

Bovine spongiform encephalopathy (BSE) is the only animal prion disease that has been demonstrated to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans. The link between BSE and vCJD was established by careful surveillance, epidemiologic investigations, and experimental studies using in vivo and in vitro models of cross-species transmission. Similar approaches have been used to assess the zoonotic potential of other animal prion diseases, including atypical forms identified through active surveillance. There is no epidemiologic evidence that classical or atypical scrapie, atypical forms of BSE, or chronic wasting disease (CWD) is associated with human prion disease, but the limitations of the epidemiologic data should be taken into account when interpreting these results. Transmission experiments in nonhuman primates and human PrP transgenic mice suggest that classic scrapie, L-type atypical BSE (L-BSE), and CWD may have zoonotic potential, which for L-BSE appears to be equal to or greater than that of classic BSE. The results of in vitro conversion assays to analyze the human transmission barrier correlate well with the in vivo data. However, it is still difficult to predict the likelihood that an animal prion disease will transmit to humans under conditions of field exposure from the results of in vivo or in vitro experiments. This emphasizes the importance of continuing systematic surveillance for both human and animal prion diseases in identifying zoonotic transmission of diseases other than classic BSE.

Exploring the experiences of patients attending day hospitals in the rural Scotland: capturing the patient's voice.

AIMS AND OBJECTIVES: To understand the meaning of person-centred compassionate care for people attending day hospitals in rural Scotland. BACKGROUND: Increasing numbers of older people are living with chronic conditions and require support to live at home. Intermediate care services such as day hospitals can enable this. Much previous research about day hospitals focused on organisational aspects of care. This study set out to capture the voice of the patient using this service. DESIGN: A descriptive qualitative study. METHODS: Individual interviews were undertaken in participant's homes using emotional touchpoints as prompts to help patients discuss their experience of care within a day hospital (n = 15). Data were analysed using thematic analysis. RESULTS: Four main themes were identified from the data: Relationships, Feeling Valued, Expectations and Perceived Benefits. The findings showed that relationships with staff and other patients were important. The patients also wanted to feel valued, and helping others was part of this. The patients had clear expectations of the service but had an acute awareness of the benefits of attending the day hospital such as coordination of their care. Overall, the patients were highly satisfied, felt that care was person-centred and recognised the advantages of remaining close to home. CONCLUSIONS: At a time when enabling health and social care integration is a priority, this study provides insight into the patient perspective of intermediate care. The findings reveal what matters to patients cared for in the community and how this service can respond to this. RELEVANCE TO CLINICAL PRACTICE: This study provides insight for healthcare practitioners caring for patients in the community and those responsible for planning and resourcing this service. It should also start a dialogue about how these services could be used more.

Decontamination treatments to eliminate problem biota from macroalgal tank cultures of Osmundea pinnatifida, Palmaria palmata and Ulva lactuca.

The effect of a range of chemical disinfectants at different concentration and exposure times was investigated on five macroalgal species and the marine gastropod Littorina spp. Palmaria palmata, Osmundea pinnatifida and Ulva lactuca are commercially valuable and are often cultivated in tanks for food or feed. Ectocarpus siliculosus and Ulva intestinalis are common epiphytes of P. palmata and O. pinnatifida cultures, whilst Littorina spp. are common herbivorous epibionts within U. lactuca culture tanks. These contaminants reduce the productivity and quality of the culture as a food. Differential tolerance to the treatments was seen between the algal species using pulse-amplitude modulation (PAM) chlorophyll a fluorescence, a few hours and a week following treatment. We identified treatments that selectively damaged the epiphyte but not the basiphyte species. Ectocarpus siliculosus had a significantly lower tolerance to 1 % sodium hypochlorite than P. palmata, and to 25 % methanol than O. pinnatifida, with a 1-5 min exposure appearing most suitable. Ulva intestinalis had a significantly lower tolerance than P. palmata and O. pinnatifida to many disinfectants: 0.1-1 % sodium hypochlorite for 10 min, 0.5 % potassium iodide for up to 10 min, and 0.25 % Kick-start (a commercial aquaculture disinfectant solution) for 1-5 min. No treatment was able to kill the gastropod snails without also damaging U. lactuca, although agitation in freshwater for an hr may cause them to detach from the basiphyte, with little to no photophysiological impact seen to U. lactuca. This experiment forms the basis for more extended commercial trials.

Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6-8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved into a new flock.

Susceptibility of young sheep to oral infection with bovine spongiform encephalopathy decreases significantly after weaning.

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) (or prion disease) that is readily transmissible to sheep by experimental infection and has the shortest incubation period in animals with the ARQ/ARQ PRNP genotype (at codons 136, 154, and 171). Because it is possible that sheep in the United Kingdom could have been infected with BSE by being fed contaminated meat and bone meal supplements at the same time as cattle, there is considerable interest in the responses of sheep to BSE inoculation. Epidemiological evidence suggests that very young individuals are more susceptible to TSE infection; however, this has never been properly tested in sheep. In the present study, low doses of BSE were fed to lambs of a range of ages (~24 h, 2 to 3 weeks, 3 months, and 6 months) and adult sheep. The incidence of clinical BSE disease after inoculation was high in unweaned lambs (~24 h and 2 to 3 weeks old) but much lower in older weaned animals The incubation period was also found to be influenced by the genotype at codon 141 of the PRNP gene, as lambs that were LF heterozygotes had a longer mean incubation period than those that were homozygotes of either type. The results suggest that sheep in the United Kingdom would have been at high risk of BSE infection only if neonatal animals had inadvertently ingested contaminated supplementary foodstuffs.

An economic evaluation of preclinical testing strategies compared to the compulsory scrapie flock scheme in the control of classical scrapie.

Cost-benefit is rarely combined with nonlinear dynamic models when evaluating control options for infectious diseases. The current strategy for scrapie in Great Britain requires that all genetically susceptible livestock in affected flocks be culled (Compulsory Scrapie Flock Scheme or CSFS). However, this results in the removal of many healthy sheep, and a recently developed pre-clinical test for scrapie now offers a strategy based on disease detection. We explore the flock level cost-effectiveness of scrapie control using a deterministic transmission model and industry estimates of costs associated with genotype testing, pre-clinical tests and the value of a sheep culled. Benefit was measured in terms of the reduction in the number of infected sheep sold on, compared to a baseline strategy of doing nothing, using Incremental Cost Effectiveness analysis to compare across strategies. As market data was not available for pre-clinical testing, a threshold analysis was used to set a unit-cost giving equal costs for CSFS and multiple pre-clinical testing (MT, one test each year for three consecutive years). Assuming a 40% within-flock proportion of susceptible genotypes and a test sensitivity of 90%, a single test (ST) was cheaper but less effective than either the CSFS or MT strategies (30 infected-sales-averted over the lifetime of the average epidemic). The MT strategy was slightly less effective than the CSFS and would be a dominated strategy unless preclinical testing was cheaper than the threshold price of £6.28, but may be appropriate for flocks with particularly valuable livestock. Though the ST is not currently recommended, the proportion of susceptible genotypes in the national flock is likely to continue to decrease; this may eventually make it a cost-effective alternative to the MT or CSFS.

Prion diseases are efficiently transmitted by blood transfusion in sheep.

The emergence of variant Creutzfeld-Jakob disease, following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly high transmission rates by transfusion of 36% for BSE and 43% for scrapie. A proportion of BSE-infected transfusion recipients (3 of 8) survived for up to 7 years without showing clinical signs of disease. The majority of transmissions resulted from blood collected from donors at more than 50% of the estimated incubation period. The high transmission rates and relatively short and consistent incubation periods in clinically positive recipients suggest that infectivity titers in blood were substantial and/or that blood transfusion is an efficient method of transmission. This experiment has established the value of using sheep as a model for studying transmission of variant Creutzfeld-Jakob disease by blood products in humans.

alpha-Hemoglobin stabilizing protein is not a suitable marker for a screening test for variant Creutzfeldt-Jakob disease.

BACKGROUND: A test is needed to identify blood donors who are in the preclinical phase of variant Creutzfeldt-Jakob disease (CJD). alpha-Hemoglobin stabilizing protein (AHSP; syn. ERAF, EDRF) transcript levels are reduced in the blood of mice incubating transmissible spongiform encephalopathy. STUDY DESIGN AND METHODS: Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to measure AHSP transcript and protein levels in normal blood donors, patients with CJD, and patients with other neuronal and hematologic diseases. Temporal AHSP expression was measured in sheep incubating bovine spongiform encephalopathy (BSE). RESULTS: Quantitation of AHSP in peripheral blood from normal blood donors revealed that protein levels, but not transcript levels, are influenced by sex with higher levels found in males, suggesting posttranslational regulation involving the product of an X-linked gene. When AHSP mRNA and protein levels were quantitated in peripheral blood from patients with variant and sporadic CJD, no consistent differences from normal were found. Serial quantitation of AHSP in individual BSE-infected sheep did not reveal any disease-related changes. CONCLUSION: We conclude that quantitation of AHSP is not likely to be useful for detection of preclinical prion disease in man.

Ovine prion protein variant A(136)R(154)L(168)Q(171) increases resistance to experimental challenge with bovine spongiform encephalopathy agent.

Susceptibility and incubation periods of transmissible spongiform encephalopathies, such as scrapie in sheep, are modulated by the PrP gene. The standard model of association between ovine PrP genetics and classical scrapie susceptibility is based on PrP genotypes with respect to codons 136, 154 and 171, e.g. alanine-arginine-glutamine (ARQ). It is demonstrated here that a proline to leucine substitution in codon 168 of the ovine PrP protein gene is associated with increased resistance to experimental bovine spongiform encephalopathy (BSE) inoculation. The ARL(168)Q PrP allele was found in heterozygous ARP(168)Q/ARL(168)Q sheep that have so far survived intravenous BSE challenge three times longer than BSE-challenged homozygous ARP(168)Q/ARP(168)Q sheep, which develop disease in around 700 days. In contrast, the L141F polymorphism does not appear to be associated with susceptibility to intravenous BSE challenge.

A novel, resistance-linked ovine PrP variant and its equivalent mouse variant modulate the in vitro cell-free conversion of rPrP to PrP(res).

Prion diseases are associated with the conversion of the normal cellular prion protein, PrP(c), to the abnormal, disease-associated form, PrP(Sc). This conversion can be mimicked in vitro by using a cell-free conversion assay. It has recently been shown that this assay can be modified to use bacterial recombinant PrP as substrate and mimic the in vivo transmission characteristics of rodent scrapie. Here, it is demonstrated that the assay replicates the ovine polymorphism barriers of scrapie transmission. In addition, the recently identified ovine PrP variant ARL(168)Q, which is associated with resistance of sheep to experimental BSE, modulates the cell-free conversion of ovine recombinant PrP to PrP(res) by three different types of PrP(Sc), reducing conversion efficiencies to levels similar to those of the ovine resistance-associated ARR variant. Also, the equivalent variant in mice (L(164)) is resistant to conversion by 87V scrapie. Together, these results suggest a significant role for this position and/or amino acid in conversion.

The neuropathologic phenotype of experimental ovine BSE is maintained after blood transfusion.

Iatrogenic transmission by blood transfusion has been described in cases of human variant Creutzfeldt-Jakob disease (vCJD), experimental ovine bovine spongiform encephalopathy (BSE), and natural sheep scrapie, demonstrating that blood in these prion diseases is infectious. However, the possible effect of the transfusion, derived from differences in the inoculum (blood) and the route of infection (intravenous), on the pathologic phenotype of the disease in the recipients is not known. This study describes the neuropathologic phenotype of PrP(d) accumulation in sheep succumbing to neurologic disease after blood transfusion from donors experimentally infected with BSE; these were either clinically or subclinically affected at the time of donation. We demonstrate that blood can become infectious at early stages of ovine BSE infection and that the PrP(d) immunohistochemical phenotype is maintained after transfusion. This suggests that a change in the pathologic phenotype of vCJD would not be expected as a result of exposure to infected blood.

Phenotype of disease-associated PrP accumulation in the brain of bovine spongiform encephalopathy experimentally infected sheep.

In view of the established link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease and of the susceptibility of sheep to experimental BSE, the detection of potential cases of naturally occurring BSE in sheep has become of great importance. In this study, the immunohistochemical (IHC) phenotype of disease-associated prion protein (PrP(d)) accumulation has been determined in the brain of 64 sheep, of various breeds and PrP genotypes, that had developed neurological disease after experimental BSE challenge with different inocula by a range of routes. Sheep BSE was characterized by neuron-associated intra- and extracellular PrP(d) aggregates and by conspicuous and consistent deposits in the cytoplasm of microglia-like cells. The stellate PrP(d) type was also prominent in most brain areas and marked linear deposits in the striatum and midbrain were distinctive. Sheep of the ARR/ARR and ARQ/AHQ genotypes displayed lower levels of PrP(d) than other sheep, and intracerebral BSE challenge resulted in higher levels of PrP(d) accumulating in the brain compared with other routes. The PrP genotype and the route of challenge also appeared to affect the incubation period of the disease, giving rise to complex combinations of magnitude of PrP(d) accumulation and incubation period. Despite these differences, the phenotype of PrP(d) accumulation was found to be very consistent across the different factors tested (notably after subpassage of BSE in sheep), thus highlighting the importance of detailed IHC examination of the brain of clinically affected sheep for the identification of potential naturally occurring ovine BSE.

Immunohistochemical characteristics of disease-associated PrP are not altered by host genotype or route of inoculation following infection of sheep with bovine spongiform encephalopathy.

It has previously been reported that disease-associated prion protein (PrP(d)) derived from natural scrapie and from sheep infected experimentally with bovine spongiform encephalopathy (BSE) differed in respect of their immunohistochemical and immunoblotting properties. For BSE, however, these initial observations were restricted to orally challenged sheep of the ARQ/ARQ PrP genotype. Here, extended examinations were performed on 28 sheep that developed neurological signs after BSE experimental infection by one of three routes. Intracerebrally infected ARQ/ARQ sheep showed more widespread and abundant accumulations of PrP(d) in tissues of the lymphoreticular system (LRS) than VRQ/VRQ animals, whereas no peripheral PrP(d) was detected in ARR/ARR sheep. The intensity and dissemination of PrP(d) accumulation in LRS tissues were less than those found previously in orally dosed sheep. AHQ/AHQ sheep challenged orally and ARQ/AHQ and ARQ/ARQ animals infected intravenously showed similar LRS-tissue PrP(d) distributions and levels to those of ARQ/ARQ sheep infected intracerebrally. The patterns of intra- and extracellular immunoreactivity to different PrP antibodies in brain and LRS tissues and the immunoblotting characteristics of PrP(res) from brain samples remained constant, irrespective of the route of inoculation and the PrP genotype, and were the same as described previously for ARQ/ARQ sheep dosed orally with BSE. These results suggest that the intracellular truncation of BSE PrP(d) and the proteinase K cleavage site of BSE PrP(res) are not altered by PrP genotype or by route of inoculation and that, therefore, screening tests based on these properties can be applied to identify potential sheep BSE cases occurring naturally.

Role of the CD40 locus in Graves' disease.

The genetic basis for Graves' disease remains largely unknown, but significant linkage to microsatellite markers on 20q11 suggests that this region harbors a susceptibility gene. One obvious candidate gene at this 20q11 locus is CD40, which encodes a B-cell-surface receptor that is involved in T-cell to B-cell signaling and is implicated in control of T-cell autoreactivity. In addition, an allele of a single nucleotide polymorphism (SNP) in the Kozak consensus sequence of the 5' untranslated region of CD40 exon 1 has been reported to show modest evidence for association with Graves' disease. We have investigated the role of this 5' untranslated region (5' UTR) in Graves' disease susceptibility in our cohort of 451 unrelated white subjects with Graves' disease and 446 healthy controls. The CD40 5'UTR SNP (C --> T, position -1) was polymerase chain reaction (PCR)amplified and genotyped using the restriction enzyme NcoI. The frequency of the C allele was 74.8% in Graves' probands compared to 75.1% in controls (not significant [NS]). We find no evidence to support allelic association with Graves' disease at this CD40 SNP, despite the adequate power of the study. We are unable to confirm a role for CD40 in Graves' disease pathogenesis in our U.K. population, however, further studies involving larger patient cohorts and a saturated SNP marker map are required to resolve this issue.

Architecture of secondary lymphoid tissue in sheep experimentally challenged with scrapie.

Scrapie is a transmissible spongiform encephalopathy in which there is an accumulation of the abnormal form of the prion protein, PrPsc, in the lymphoreticular system and nervous system. There is a particular accumulation of PrPsc on follicular dendritic cells within the germinal centre of B-cell follicles. Because accumulation of PrPsc in the nervous system leads to neuronal cell loss we have examined PrPsc accumulation in the prescapular and mesenteric lymph nodes in relation to lymph node architecture of scrapie-challenged sheep. We demonstrate that an accumulation of PrPsc in the lymph node fails to result in gross defects in the microanatomy and phenotype of T- and B-cell areas in the lymph nodes.