Exosomal cancer immunotherapy is independent of MHC molecules on exosomes

Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigen-specific T cells. Therefore, we investigated the relative importance of exosomal major histocompatibility complex (MHC) class I for the induction of antigen-specific T cell responses and tumour protection. We show that ovalbumin-loaded dendritic cell-derived exosomes from MHCI-/- mice induce antigen-specific T cells at the same magnitude as wild type exosomes. Furthermore, exosomes lacking MHC class I, as well as exosomes with both MHC class I and II mismatch, induced tumour infiltrating T cells and increased overall survival to the same extent as syngeneic exosomes in B16 melanoma. In conclusion, T cell responses are independent of exosomal MHC/peptide complexes if whole antigen is present. This establishes the prospective of using impersonalised exosomes, and will greatly increase the feasibility of designing exosome-based vaccines or therapeutic approaches in humans

Affect-matching music improves cognitive performance in adults and young children for both positive and negative emotions

Three experiments assessed the hypothesis that cognitive benefits associated with exposure to music only occur when the perceived emotion expression of the music and the participant’s affective state match. Experiment 1 revealed an affect-matching pattern modulated by gender when assessing high-arousal states of opposite valence (happy/angry) in an adult sample (n=94) in which mood classification was based on self-report, and affective valence in music was differentiated by mode and other expressive cues whilst keeping tempo constant (139 BPM). The affect-matching hypothesis was then tested in two experiments with children using a mood-induction procedure: Experiment 2 tested happy/angry emotions with, respectively, 3-5- (n=40) and 6-9-year-old (n=40) children, and Experiment 3 compared happy/sad emotions (i.e., states differing both for valence and arousal profiles) with 3-5-year-old children (n=40), using music pieces differentiated also by fast vs. slow tempo. While young children failed to discriminate systematically between fast tempo music conveying different emotions, they did display cognitive benefits from exposure to affect-matching music when both valence (e.g., mode) and arousal level (e.g., tempo) differentiated the musical excerpts, with no gender effects

A ‘near‐life experience’: lived experiences of spirituality from the perspective of people who have been subject to inpatient psychiatric care

Aims: To describe lived experiences of spirituality from the perspective of people who have been subject to inpatient psychiatric care and to interpret these experiences from an understanding of health as dialectical. Methods: After approval from a regional ethical board,eleven participants were recruited from two organisations for people with mental health problems. Participants were asked to narrate about spiritual experiences and occasions where such experiences had come close. The transcribed interviews were analysed by means of a phenomenological hermeneutical approach. Findings: A structural analysis of the text resulted in three themes; perceiving the presence of something extra mundane, making sense of reality and struggling for acceptance. The comprehensive understanding highlights spiritual experiences as going beyond religion, even though religious experiences appear as part of it. These experiences can indeed be a resource contributing to experiences of hope, connectedness, meaning and coherence in life. However, they can also give rise to doubt, anxiety and feelings of loneliness and hopelessness. Rather than understanding spiritual experiences as being either ‘good’ or ‘bad’, we could approach spirituality as something that is always present in alternate and inter-related forms. Metaphorically, this could be understood as a ‘near-life experience’, summarising participants’experiences related to their struggle with issues related to suffering and health which are simultaneously present. Conclusions: If psychiatric nurses could approach this complexity and, without being judgemental, explore seemingly positive and negative experiences of spirituality as dialectically related to each other, rather than viewing them as either resources or problems, this could contribute to insiderness care and hopefully also support people who struggle with these experiences to seek help when needed

Ammonia formation over Pd/Al2O3 modified with cerium and barium

We report experimental results for ammonia formation from nitric oxide and either a direct source of hydrogen or from a mixture of carbon monoxide and water over palladium based catalysts. Specifically, the addition of barium or cerium into an alumina supported palladium sample was studied. Static and transient flow reactor experiments were performed in order to identify the effects of temperature and the presence of oxygen on the activity for ammonia formation. Modification of Pd/Al2O3 with cerium proved to be beneficial for the activity due mainly to its enhancement of the water-gas-shift reaction, thus providing a higher availability of hydrogen for ammonia formation, but also because it remains active in the presence of slightly oxidizing global conditions when hydrogen is provided directly to the feed. Although the modification of Pd/Al2O3 with barium did not affect the ammonia formation during static conditions, the activity during lean/rich cycling increased. This is important for applications of passive selective catalytic reduction

Designing and managing music festival experiences to enhance attendees’ psychological and social benefits

Attendance and participation at popular music festivals has become an important and increasingly common experience for people in many Western societies, yet little is known about the kinds of benefits visitors perceive they gain as a result of attending. This research explores attendees’ perceptions of the psychological and social benefits associated with their attendance of the Woodford Folk Music Festival in Queensland (Australia). Based upon the research findings, music festival management strategies are suggested to improve the design of festival experiences to better cater to the artistic, musical, social and psychological needs of attendees thereby increasing the impact and depth of the experience

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats

Awareness of social care needs in people with epilepsy and intellectual disability

Background: Nearly a quarter of people with intellectual disability (ID) have epilepsy with large numbers experiencing drug-resistant epilepsy, and premature mortality. To mitigate epilepsy risks the environment and social care needs, particularly in professional care settings, need to be met. Purpose: To compare professional care groups as regards their subjective confidence and perceived responsibility when managing the need of people with ID and epilepsy. Method: A multi-agency expert panel developed a questionnaire with embedded case vignettes with quantitative and qualitative elements to understand training and confidence in the health and social determinants of people with ID and epilepsy. The cross-sectional survey was disseminated amongst health and social care professionals working with people with ID in the UK using an exponential non-discriminative snow-balling methodology. Group comparisons were undertaken using suitable statistical tests including Fisher's exact, Kruskal-Wallis, and Mann-Whitney. Bonferroni correction was applied to significant (p < 0.05) results. Content analysis was conducted and relevant categories and themes were identified. Results: Social and health professionals (n = 54) rated their confidence to manage the needs of people with ID and epilepsy equally. Health professionals showed better awareness (p < 0.001) of the findings/recommendations of the latest evidence on premature deaths and identifying and managing epilepsy-related risks, including the relevance of nocturnal monitoring. The content analysis highlighted the need for clearer roles, improved care pathways, better epilepsy-specific knowledge, increased resources, and better multi-disciplinary work. Conclusions: A gap exists between health and social care professionals in awareness of epilepsy needs for people with ID, requiring essential training and national pathways

The long-term psycho-social impact of the pandemic on people with intellectual disability and their carers

Background: People with intellectual disabilities (PWID) are at six times higher risk of death due to COVID-19. To mitigate harm, as a high-risk group, significant social changes were imposed on PWID in the UK. Alongside these changes, the uncertainty of the pandemic influence, caused PWID and their carers to encounter significant stress. The evidence of the pandemic’s psycho-social impact on PWID originates mainly from cross-sectional surveys conducted with professionals and carers. There is little research on the longitudinal psycho-social impact of the pandemic from PWID themselves. Aims: To examine the long-term psycho-social impact of the pandemic on PWID. Methods: A cross-sectional survey, following STROBE guidance, of 17 Likert scale statements (12 to PWID and 5 to their carers) to ascertain the pandemic’s psychosocial impact was conducted. Every other PWID open to a specialist Intellectual Disability service serving half a UK County (pop:500,000) was selected. The same survey was re-run with the same cohort a year later. Descriptive statistics, Mann-Whitney, Chi-square and unpaired-t tests were used to compare responses. Significance is taken at p &lt; .05. Comments were analysed using Clarke and Braun’s approach. Results: Of 250 PWID contacted, 100 (40%) responded in 2020 and 127 (51%) in 2021. 69% (2020) and 58% (2021) reported seeking medical support. Carers, (88%, 2020 and 90%, 2021) noticed emotional changes in PWID they cared for. 13% (2020) and 20% (2021) of PWID had their regular psychotropics increased. 21% (2020) and 24% (2021) had their pro re nata (PRN) medication adjusted. PWID or carers demonstrated no statistically significant variation in responses between themselves from 2020 to 2021. PWID were more likely to report being upset/distressed compared to their carers’ perceptions of them in both years ( p &lt; .001). Four themes were identified. Conclusion: This longitudinal study highlights the diverse psycho-social impact of the pandemic on PWID in the UK. The Pandemic’s psycho-social impact has been significantly underestimated. </jats:sec