Implying implausibility and undermining versus accepting peoples' experiences of suicidal ideation and self-harm in Emergency Department psychosocial assessments.

Background: Patients seeking emergency care for self-harm and suicidality report varying experiences from being believed and taken seriously to not being believed and taken seriously. Epistemic injustice provides a conceptual framework to explore how peoples' experiences of self-harm and suicidality are believed or not. We use an empirical method -conversation analysis - to analyze epistemics in clinical communication, focusing on how knowledge is claimed, contested and negotiated. In courtroom, police and political interaction, conversation analysis has identified communication practices implying implausibility in a person's story to contest and recharacterize their accounts. Aims: To investigate communication practices in Emergency Department (ED) biopsychosocial assessments that may (1) undermine, imply implausibility and recharacterize or (2) accept peoples' experiences of suicidal ideation and self-harm. Methods: Using conversation analysis, we micro-analyzed verbal and non-verbal communication in five video-recorded biopsychosocial assessments with people presenting to the ED with self-harm or suicidal ideation, and conducted supplementary analysis of participants' medical records and post-visit interviews. We present three cases where experiences were not accepted and undermined/recharacterized and two cases where experiences were accepted and validated. Results: When peoples' experiences of suicidality and self-harm were not accepted or were undermined, questioners: did not acknowledge or accept the person's account; asked questions that implied inconsistency or implausibility ("Didn't you tell your GP that you were coping okay?"); juxtaposed contrasting information to undermine the person's account ("You said you were coping okay before, and now you're saying you feel suicidal"); asked questions asserting that, e.g., asking for help implied they were not intending to end their life ("So when you called 111 what were you expecting them to do"); and resistinged or directly questioned the person's account. Multiple practices across the assessment built on each other to assert that the person was not suicidal, did not look or act like they were suicidal; that the person's decision to attend the ED was not justified; that an overdose was impulsive and not intended to end life; asking why the person didn't take a more harmful medication to overdose; that self-harming behaviors were not that serious and should be in the person's control. Alternative characterizations were used to justify decisions not to provide further support or referrals to specialist services. At times, these practices were also delivered when speaking over the patient. When peoples' experiences were accepted, practitioners acknowledged, accepted, validated suicidality/self-harm and introduced a shared understanding of experiences that patients found helpful. Non-verbal feedback such as nodding and eye contact was central in acceptance of patients' accounts. Conclusion: These findings advance our understanding of how peoples' experiences of suicidality or self-harm are undermined or accepted in mental health encounters in the ED. They have important clinical implications: patients report that when their experiences are not accepted or undermined, this makes them more distressed, less hopeful about the future and discourages future help-seeking when in crisis. Conversely, acknowledging, accepting and validating suicidality/self-harm and introducing a new ways of understanding peoples' experiences may make people less suicidal and more hopeful, generates shared understanding and encourages future help-seeking.

Temporal trends in eating disorder and self-harm incidence rates among adolescents and young adults in the UK in the 2 years since onset of the COVID-19 pandemic: a population-based study.

BACKGROUND: Self-harm and eating disorders share multiple risk factors, with onset typically during adolescence or early adulthood. We aimed to examine the incidence rates of these psychopathologies among young people in the UK in the 2 years following onset of the COVID-19 pandemic. METHODS: We conducted a population-based study using the primary care electronic health records of patients aged 10-24 years in the UK Clinical Practice Research Datalink (CPRD). The observation period was from Jan 1, 2010, to March 31, 2022. We calculated the monthly incidence rates of eating disorders and self-harm according to the first record of each outcome. On the basis of antecedent trends between January, 2010, and February, 2020, negative binomial regression models were fitted to predict monthly incidence rates after the pandemic began in March, 2020. Percentage differences between observed and expected incidence were calculated to indicate changes since the onset of the pandemic, with stratification by sex, age, and deprivation quintile. FINDINGS: The primary care health records of 9 184 712 patients aged 10-24 years (4 836 226 [52·7%] female patients and 4 348 486 [47·3%] male patients; n=1881 general practices) were included for analysis. The incidence rates of eating disorders and self-harm among girls were higher than expected between March 1, 2020, and March 31, 2022. The observed incidence of eating disorders was 42·4% (95% CI 25·7-61·3) higher than expected for girls aged 13-16 years, and 32·0% (13·3-53·8) higher than expected for girls aged 17-19 years, whereas other age groups showed little difference between observed and expected incidence. Similarly, the increase in self-harm incidence was driven by girls aged 13-16 years, for whom the observed incidence was 38·4% (20·7-58·5) higher than expected. By contrast, among boys in all age groups, the incidence rates of eating disorders and self-harm were lower than, or close to, the expected rates. Among boys, the observed incidence of eating disorders was 22·8% (9·2-34·4) lower than expected, and the observed incidence of self-harm was 11·5% (3·6-18·7) lower than expected. The estimated increases in eating disorder and self-harm incidence among girls aged 13-16 years were largely attributable to increases within less deprived communities. INTERPRETATION: Although causes are uncertain, increased incidence of eating disorder diagnoses and self-harm among teenage girls in the UK during the first 2 years of the COVID-19 pandemic highlight an urgent need for intervention. Early identification of mental health difficulties by primary care clinicians is necessary. Timely access to treatments and sufficient support from general practitioners and mental health services needs to be available to manage presenting problems and to prevent exacerbations of conditions. FUNDING: National Institute for Health and Care Research.

A qualitative study exploring the benefits of involving young people in mental health research.

INTRODUCTION: It is increasingly accepted that young people need to be centrally involved in research on issues that affect them. The aim of this study was to explore young people's perceptions of the benefits for them of being involved in mental health research and the processes that enabled these benefits. METHODS: Qualitative interviews were conducted by co-researchers (young people with lived experience and/or interest in mental health) with 13 young people (aged 13-24 years) who had experience of being involved in mental health research when they were between 11 and 16 years of age. Reflective thematic analysis was used to identify important aspects of young people's experiences. RESULTS: Four main themes were identified: (1) opportunity to have a meaningful impact, (2) opportunity to be part of a supportive community, (3) opportunity to learn and grow and (4) increasing opportunities for young people. CONCLUSION: This study highlights young people's experiences of being involved in mental health research and identifies ways in which researchers can ensure that involvement opportunities bring benefits to both the young people and the research. PATIENT OR PUBLIC CONTRIBUTION: This research was a response to issues raised by young people involved in research. The project was supported by co-researchers throughout, including design, data collection, analysis and write-up.

New insight into Epstein-Barr virus infection using models of stratified epithelium.

Epstein-Barr virus (EBV) is a ubiquitous human pathogen that is transmitted in saliva. EBV transits through the oral epithelium to infect B cells, where it establishes a life-long latent infection. Reinfection of the epithelium is believed to be mediated by virus shed from B cells, but whether a latent reservoir can exist in the epithelia is unknown. We previously developed an in vitro organotypic model of stratified epithelium where EBV can readily replicate within the suprabasal layers of the epithelium following apical infection mediated by virus-producing B cells. Given that infected epithelial cells and cell-free virus are observed in saliva, we examined the ability of both of these to mediate infection in organotypic cultures. Epithelial-derived cell-free virus was able to infect organotypic cultures from the apical surface, but showed enhanced infection of B cells. Conversely, B cell-derived virus exhibited enhanced infection of epithelial cells. While EBV has been detected in basal cells in oral hairy leukoplakia, it is unknown whether EBV can be seen in undifferentiated primary keratinocytes in the basal layer. Undifferentiated epithelial cells expressed proposed EBV receptors in monolayer and were susceptible to viral binding and entry. Integrins, and occasionally ephrin A2, were expressed in the basal layer of gingiva and tonsil derived organotypic cultures, but the known B-cell receptors HLAII and CD21 were not detected. Following infection with cell-free virus or virus-producing B cells at either the apical or basolateral surface of preformed organotypic cultures, abundant infection was detected in differentiated suprabasal cells while more limited but readily detectable infection was observed in the undifferentiated basal cells. Together, our data has provided new insight into EBV infection in stratified epithelium.

The Epstein-Barr Virus Glycoprotein BDLF2 Is Essential for Efficient Viral Spread in Stratified Epithelium.

Epstein-Barr virus (EBV) is a ubiquitous human pathogen that infects the majority of the adult population regardless of socioeconomic status or geographical location. EBV primarily infects B and epithelial cells and is associated with different cancers of these cell types, such as Burkitt lymphoma and nasopharyngeal carcinoma. While the life cycle of EBV in B cells is well understood, EBV infection within epithelium is not, largely due to the inability to model productive replication in epithelium in vitro. Organotypic cultures generated from primary human keratinocytes can model many aspects of EBV infection, including productive replication in the suprabasal layers. The EBV glycoprotein BDLF2 is a positional homologue of the murine gammaherpesvirus-68 protein gp48, which plays a role in intercellular spread of viral infection, though sequence homology is limited. To determine the role that BDLF2 plays in EBV infection, we generated a recombinant EBV in which the BDLF2 gene has been replaced with a puromycin resistance gene. The ΔBDLF2 recombinant virus infected both B cell and HEK293 cell lines and was able to immortalize primary B cells. However, the loss of BDLF2 resulted in substantially fewer infected cells in organotypic cultures compared to wild-type virus. While numerous clusters of infected cells representing a focus of infection are observed in wild-type-infected organotypic cultures, the majority of cells observed in the absence of BDLF2 were isolated cells, suggesting that the EBV glycoprotein BDLF2 plays a major role in intercellular viral spread in stratified epithelium. IMPORTANCE The ubiquitous herpesvirus Epstein-Barr virus (EBV) is associated with cancers of B lymphocytes and epithelial cells and is primarily transmitted in saliva. While several models exist for analyzing the life cycle of EBV in B lymphocytes, models of EBV infection in the epithelium have more recently been established. Using an organotypic culture model of epithelium that we previously determined accurately reflects EBV infection in situ, we have ascertained that the loss of the viral envelope protein BDLF2 had little effect on the EBV life cycle in B cells but severely restricted the number of infected cells in organotypic cultures. Loss of BDLF2 has a substantial impact on the size of infected areas, suggesting that BDLF2 plays a specific role in the spread of infection in stratified epithelium.

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.

Communication in youth mental health clinical encounters: Introducing the agential stance.

When young people seek support from mental health care practitioners, the encounters may affect the young people's sense of self, and in particular undermine their sense of agency. For this study, an interdisciplinary team of academics and young people collaboratively analysed video-recorded encounters between young people and mental healthcare practitioners in emergency services. They identified five communication techniques that practitioners can use to avoid undermining the young person's sense of agency in the clinical encounter. They conceptualise the use of those techniques as the adoption of an agential stance towards the young person. The agential stance consists of: (a) validating the young person's experiences, (b) legitimising the young person's choice to seek help, (c) refraining from objectifying the young person, (d) affirming the young person's capacity to contribute to positive change, and (e) involving the young person in the decision-making process.

Priorities for Future Research About Screen Use and Adolescent Mental Health: A Participatory Prioritization Study.

Introduction: This study aimed to identify research priorities for future research on screen use and adolescent mental health, from the perspectives of young people, parents/carers, and teachers. Methods: The study design was informed by the James Lind Alliance Priority Setting Partnership approach. A three-stage consensus-based process of consultation to identify research priorities using qualitative and quantitative methods. Research was guided by a steering group comprising researchers, third sector partners, clinicians, parents/carers and young people. A Young People's Advisory Group contributed at each stage. Results: Initial steps generated 26 research questions of importance to children and young people; these were ranked by 357 participants (229 children and young people and 128 adults). Consensus was reached for the prioritization of four topics for future research: (i) the impact of exposure to adult content on young people's mental health and relationships; (ii) the relationship between screen use and the well-being of young people from vulnerable groups; (iii) the impact of screen use on brain development; and (iv) the relationship between screen use and sleep.Additionally, young participants prioritized questions about online bullying, advertisements targeting young people, and the relationship between social media and specific mental health conditions. Research topics of interest arising specifically during the pandemic included the effects on adolescent mental health of exposure to constant news updates and online racial bias, and how young people take part in activism online. Conclusion: These findings will enable researchers and funders to conduct research that is needs-oriented and relevant to the target audience.

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.

Host Lung Environment Limits Aspergillus fumigatus Germination through an SskA-Dependent Signaling Response.

Aspergillus fumigatus isolates display significant heterogeneity in growth, virulence, pathology, and inflammatory potential in multiple murine models of invasive aspergillosis. Previous studies have linked the initial germination of a fungal isolate in the airways to the inflammatory and pathological potential, but the mechanism(s) regulating A. fumigatus germination in the airways is unresolved. To explore the genetic basis for divergent germination phenotypes, we utilized a serial passaging strategy in which we cultured a slow germinating strain (AF293) in a murine-lung-based medium for multiple generations. Through this serial passaging approach, a strain emerged with an increased germination rate that induces more inflammation than the parental strain (herein named LH-EVOL for lung homogenate evolved). We identified a potential loss-of-function allele of Afu5g08390 (sskA) in the LH-EVOL strain. The LH-EVOL strain had a decreased ability to induce the SakA-dependent stress pathway, similar to AF293 ΔsskA and CEA10. In support of the whole-genome variant analyses, sskA, sakA, or mpkC loss-of-function strains in the AF293 parental strain increased germination both in vitro and in vivo. Since the airway surface liquid of the lungs contains low glucose levels, the relationship of low glucose concentration on germination of these mutant AF293 strains was examined; interestingly, in low glucose conditions, the sakA pathway mutants exhibited an enhanced germination rate. In conclusion, A. fumigatus germination in the airways is regulated by SskA through the SakA mitogen-activated protein kinase (MAPK) pathway and drives enhanced disease initiation and inflammation in the lungs. IMPORTANCE Aspergillus fumigatus is an important human fungal pathogen particularly in immunocompromised individuals. Initiation of growth by A. fumigatus in the lung is important for its pathogenicity in murine models. However, our understanding of what regulates fungal germination in the lung environment is lacking. Through a serial passage experiment using lung-based medium, we identified a new strain of A. fumigatus that has increased germination potential and inflammation in the lungs. Using this serially passaged strain, we found it had a decreased ability to mediate signaling through the osmotic stress response pathway. This finding was confirmed using genetic null mutants demonstrating that the osmotic stress response pathway is critical for regulating growth in the murine lungs. Our results contribute to the understanding of A. fumigatus adaptation and growth in the host lung environment.

Understanding practitioners' and young people's views of a risk calculator for future psychopathology and poor functioning in young people victimised during childhood.

BACKGROUND: Although children who are exposed to victimisation (including abuse, neglect, domestic violence and bullying) have an increased risk of later psychopathology and functional impairment, not all go on to develop these outcomes. Risk calculators that generate individualised probabilities of a victimised child developing future psychopathology and poor functioning have the potential to help practitioners identify the most vulnerable children and efficiently target preventive interventions. AIM: This study explored the views of young people and practitioners regarding the acceptability and feasibility of potentially using a risk calculator to predict victimised children's individual risk of poor outcomes. METHODS: Young people (n = 6) with lived experience of childhood victimisation took part in two focus groups. Health and social care practitioners (n = 13) were interviewed individually. Focus groups and interviews were audio-recorded, transcribed and thematically analysed. RESULTS: Ten themes were identified, organised according to the three main topics of discussion: (i) identifying risk (risk factors, current practice, accuracy, implementation, response); (ii) protective factors and prevention (individual, environment, preventative intervention); and (iii) communication of research (stakeholders, methods). CONCLUSION: Risk calculators have the potential to enhance health and social care practice in the United Kingdom, but we highlight key factors that require consideration for successful implementation.

Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis.

Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how immune competent hosts maintain control of fungal infections while constantly being exposed to fungi is rapidly emerging. It is known that timely neutrophil recruitment to and activation in the lungs is critical to the host defense against development of invasive pulmonary aspergillosis, but the inflammatory sequelae necessary remains to be fully defined. Here, we show that 5-Lipoxygenase (5-LO) and Leukotriene B4 (LTB4) are critical for leukocyte recruitment and resistance to pulmonary A. fumigatus challenge in a fungal-strain-dependent manner. 5-LO activity was needed in radiosensitive cells for an optimal anti-fungal response and in vivo LTB4 production was at least partially dependent on myeloid-derived hypoxia inducible factor-1α. Overall, this study reveals a role for host-derived leukotriene synthesis in innate immunity to A. fumigatus.

Generation and Infection of Organotypic Cultures with Epstein-Barr Virus.

While numerous model systems are available to study EBV latency in B cells and have contributed greatly to our understanding of the role of these cells in the viral life cycle, models to study the EBV life cycle in epithelial cells in vitro are lacking. Epithelial cells are poorly infected in vitro, and EBV-infected cell lines have not been successfully obtained from epithelial tumors. Recently, we have demonstrated that organotypic cultures of oral keratinocytes can be used as a model to study EBV infection in the epithelial tissue. These "raft" cultures generate a stratified tissue resembling the epithelium seen in vivo with a proliferating basal layer and differentiating suprabasal layers. Here, we describe generation of EBV-infected raft cultures established from primary oral mucosal epithelial cells, which exhibit high levels of productive replication induced by differentiation, as well as methods to analyze EBV infection.

Mast cells and influenza a virus: association with allergic responses and beyond.

Influenza A virus (IAV) is a widespread infectious agent commonly found in mammalian and avian species. In humans, IAV is a respiratory pathogen that causes seasonal infections associated with significant morbidity in young and elderly populations, and has a large economic impact. Moreover, IAV has the potential to cause both zoonotic spillover infection and global pandemics, which have significantly greater morbidity and mortality across all ages. The pathology associated with these pandemic and spillover infections appear to be the result of an excessive inflammatory response leading to severe lung damage, which likely predisposes the lungs for secondary bacterial infections. The lung is protected from pathogens by alveolar epithelial cells, endothelial cells, tissue resident alveolar macrophages, dendritic cells, and mast cells. The importance of mast cells during bacterial and parasitic infections has been extensively studied; yet, the role of these hematopoietic cells during viral infections is only beginning to emerge. Recently, it has been shown that mast cells can be directly activated in response to IAV, releasing mediators such histamine, proteases, leukotrienes, inflammatory cytokines, and antiviral chemokines, which participate in the excessive inflammatory and pathological response observed during IAV infections. In this review, we will examine the relationship between mast cells and IAV, and discuss the role of mast cells as a potential drug target during highly pathological IAV infections. Finally, we proposed an emerging role for mast cells in other viral infections associated with significant host pathology.

Efficient replication of Epstein-Barr virus in stratified epithelium in vitro.

Epstein-Barr virus is a ubiquitous human herpesvirus associated with epithelial and lymphoid tumors. EBV is transmitted between human hosts in saliva and must cross the oral mucosal epithelium before infecting B lymphocytes, where it establishes a life-long infection. The latter process is well understood because it can be studied in vitro, but our knowledge of infection of epithelial cells has been limited by the inability to infect epithelial cells readily in vitro or to generate cell lines from EBV-infected epithelial tumors. Because epithelium exists as a stratified tissue in vivo, organotypic cultures may serve as a better model of EBV in epithelium than monolayer cultures. Here, we demonstrate that EBV is able to infect organotypic cultures of epithelial cells to establish a predominantly productive infection in the suprabasal layers of stratified epithelium, similar to that seen with Kaposi's-associated herpesvirus. These cells did express latency-associated proteins in addition to productive-cycle proteins, but a population of cells that exclusively expressed latency-associated viral proteins could not be detected; however, an inability to infect the basal layer would be unlike other herpesviruses examined in organotypic cultures. Furthermore, infection did not induce cellular proliferation, as it does in B cells, but instead resulted in cytopathic effects more commonly associated with productive viral replication. These data suggest that infection of epithelial cells is an integral part of viral spread, which typically does not result in the immortalization or enhanced growth of infected epithelial cells but rather in efficient production of virus.

Characterizing vancomycin-resistant enterococci in neonatal intensive care.

Repetitive sequence-based polymerase chain reaction fingerprinting was used to characterize 23 vancomycin-nonsusceptible enterococcal isolates from 2003 to 2004. Five genetically related clusters spanned geographically distinct referring centers. DNA fingerprinting showed infant-to-infant transmission from referring institutions. Thus, community healthcare facilities are a source of vancomycin-nonsusceptible enterococci and should be targeted for increased infection control efforts.