Antibody and T-Cell Subsets Analysis Unveils an Immune Profile Heterogeneity Mediating Long-term Responses in Individuals Vaccinated Against SARS-CoV-2.

BACKGROUND: Based on the fact that coronavirus disease 2019 (COVID-19) is still spreading despite worldwide vaccine administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced interindividual immune response variations. METHODS: We compared humoral and cellular immune responses in 127 individuals vaccinated with either BNT162b2, mRNA-1273, or ChAdOx1-nCoV-19 vaccine. RESULTS: Both mRNA vaccines induced faster and stronger humoral responses as assessed by high spike- and RBD-specific antibody titers and neutralizing efficacy in comparison to ChAdOx1-nCoV-19 vaccine. At 7 months postvaccination, a decreasing trend in humoral responses was observed, irrespective of the vaccine administered. Correlation analysis between anti-S1 IgG and interferon- (IFN-) production unveiled a heterogeneous immune profile among BNT162b2-vaccinated individuals. Specifically, vaccination in the high-responder group induced sizable populations of polyfunctional memory CD4 helper T cells (TH1), follicular helper T cells (TFH), and T cells with features of stemness (TSCM), along with high neutralizing antibody production that persisted up to 7 months. In contrast, low responders were characterized by significantly lower antibody titers and memory T cells and a considerably lower capacity for interleukin-2 and IFN- production. CONCLUSIONS: We identified that long-term humoral responses correlate with the individuals ability to produce antigen-specific persistent memory T-cell populations.

Evidence of two types of balance between stem cell mitosis and enterocyte nucleus growth in the Drosophila midgut.

Systemic and stem cell niche-emanating cytokines and growth factors can promote regeneration, through mitosis. High mitosis, however, predisposes for all types of cancer and, thus, a trade-off exists between regeneration capacity and tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative signaling in stem cell mitosis of adult Drosophila midgut of different genetic backgrounds. We provide evidence of two naturally occurring types of balance between mitosis and enterocyte nucleus growth: one based mostly on stem cell mitosis producing new cells and the other based mostly on the degree of young enterocyte nucleus size increase. Mitosis promotes intestinal host defense to infection, but predisposes for dysplasia in the form of stem cell-like clusters. Enterocyte nucleus growth also promotes host defense, without the drawback of promoting dysplasia. Through quantitative genetics, we identified eiger as an autocrine and paracrine inducer of stem cell mitosis. eiger expression in immature epithelial cells tilts the balance towards mitosis and dysplasia via a positive-feedback loop of highly mitotic stem cells sustaining more small nucleus enterocytes, which in turn supply more Eiger.

The COMMAND trial of cognitive therapy to prevent harmful compliance with command hallucinations: predictors of outcome and mediators of change.

BACKGROUND: Acting on harmful command hallucinations is a major clinical concern. Our COMMAND CBT trial approximately halved the rate of harmful compliance (OR = 0.45, 95% CI 0.23-0.88, p = 0.021). The focus of the therapy was a single mechanism, the power dimension of voice appraisal, was also significantly reduced. We hypothesised that voice power differential (between voice and voice hearer) was the mediator of the treatment effect. METHODS: The trial sample (n = 197) was used. A logistic regression model predicting 18-month compliance was used to identify predictors, and an exploratory principal component analysis (PCA) of baseline variables used as potential predictors (confounders) in their own right. Stata's paramed command used to obtain estimates of the direct, indirect and total effects of treatment. RESULTS: Voice omnipotence was the best predictor although the PCA identified a highly predictive cognitive-affective dimension comprising: voices' power, childhood trauma, depression and self-harm. In the mediation analysis, the indirect effect of treatment was fully explained by its effect on the hypothesised mediator: voice power differential. CONCLUSION: Voice power and treatment allocation were the best predictors of harmful compliance up to 18 months; post-treatment, voice power differential measured at nine months was the mediator of the effect of treatment on compliance at 18 months.

The effectiveness of the Penn Resiliency Programme (PRP) and its adapted versions in reducing depression and anxiety and improving explanatory style: A systematic review and meta-analysis.

Mental health problems in children can be precursors of psychosocial problems in adulthood. The aim of this study is to assess the effectiveness of the universal application of a resilience intervention (PRP and derivatives), which has been proposed for large scale roll-out. Electronic databases were searched for published randomized controlled trials of PRP and derivatives to prevent depression and anxiety and improve explanatory style in students aged 8-17 years. Studies were meta-analysed and effect sizes with confidence intervals were calculated. The Quality Assessment Tool for Quantitative Studies of the Effective Public Health Practice Project was used to determine the confidence in the effect estimates. Nine trials from Australia, the Netherlands and USA met the inclusion criteria. No evidence of PRP in reducing depression or anxiety and improving explanatory style was found. The large scale roll-out of PRP cannot be recommended. The content and structure of universal PRP should be re-considered.

The strengths based approach as a service delivery model for severe mental illness: a meta-analysis of clinical trials.

BACKGROUND: The strengths-based approach is considered a paradigm shift from the deficits- focused service delivery models. The aim of this review was to systematically review randomised controlled trials (RCTs) and quasi experimental studies examining the impact of the strengths-based approach on level of functioning and quality of life as primary outcomes and psychotic symptoms as secondary outcomes in people diagnosed with severe mental illness. METHODS: This review was conducted in the School of Health Sciences, University of Nottingham, United Kingdom. Participants in the primary studies were adults diagnosed with psychotic disorders. The methodological quality of the included studies was assessed independently by two reviewers using "Consort 2010" checklist for the randomized controlled trials or "TREND" for the quasi-experimental studies. The EPOC checklist was used for data extraction while management of data and meta-analysis were performed using Review Manager software (RevMan version 5.2). RESULTS: No significant difference was found between the strengths-based approach and other service delivery models in level of functioning and quality of life. However, a significant effect on symptoms favouring other service delivery models was reported. CONCLUSION: Based upon evidence of moderate quality, this review suggests there is no effect of the strengths-based model of service delivery in level of functioning and quality of life in adults diagnosed with severe mental illness. The number of trials is low; therefore further evidence is required to ascertain the impact of the strengths-based approach in community mental health care.

Safeguarding in adolescent mental health research: navigating dilemmas and developing procedures.

Mental disorders are prevalent during adolescence. Self-harm and suicide are more common in adolescents with a probable mental disorder, with one in four reporting to have attempted self-harm. Research involving adolescents is, therefore, likely to include participants experiencing mental ill health, even if mental health is not the primary focus. Researchers should adopt procedures and principles that safeguard adolescent mental health in their research practice. Yet there are gaps between theory and practice of research with adolescents in relation to their mental health, and limited guidance is available.We discuss emerging safeguarding dilemmas and procedures in adolescent mental health research. Our experiences of safeguarding adolescent mental health are grounded in the UK National Institute for Health and Care Research-funded SMART Schools Study. Drawing from this secondary school-based study, we focus on how our research team encountered and addressed a high prevalence of participants (aged 12-13 and 14-15 years) reporting thoughts and behaviours related to self-harm or suicide (24% of participants). This included reviewing our existing risk mitigation processes and consulting with several committees including young people with lived experiences of mental health.We present the SMART Schools study safeguarding approach for adolescent mental health. This encompasses key safeguarding principles, study procedures and relevant justifications. We address school and university roles and responsibilities, pupil understanding, and efficient, effective and secure communication pathways. We embed guidance throughout this article for researchers working with adolescents in the context of mental health. Lastly, we present five key recommendations to safeguard the mental health of adolescents participating in research, including (1) appointing a safeguarding lead within the research team; (2) codesigning a bespoke study safeguarding approach; (3) adopting a responsive approach to mental health safeguarding; (4) being transparent about the study mental health safeguarding approach and (5) report the implementation and outcomes of safeguarding approaches.Trial registration number ISRCTN77948572.

Emergency department staff experiences of working with people who self-harm: A qualitative examination of barriers to optimal care.

For people who seek help for self-harm, emergency departments (ED) are often the first point of contact, making them a suitable setting for intervention. In Australia, base rates of self-harm presentations to ED are increasing, while the quality of care these people receive is often considered sub-optimal. This study used qualitative interviews to explore potential barriers ED staff face in delivering best possible self-harm care. Seventeen staff across two EDs in the state of Victoria, Australia, were interviewed regarding their perceptions of barriers to providing optimal self-harm care and suggestions for improvement. Three themes were identified: (1) system-related challenges when managing self-harm in ED, including the shortage of hospital resources, challenges of ED as a physical environment, and insufficient education, training and guidelines about self-harm care for staff; (2) human-related challenges regarding management of self-harm in ED, which encompassed the nature of a person's circumstances and presentation, and staff attitudes towards self-harm; and (3) staff suggestions for improving self-harm care in ED. Specific recommendations that were proposed based on these findings included introducing a separate ED area for mental health-related presentations, provision of specialised education and training about self-harm care to staff, better implementation of guidelines on treating self-harm in ED, and employing mental health educators to provide on-the-floor mentoring to nurses. The relevance of these barriers and recommendations to the wider healthcare sector is also discussed. Together, these findings may inform improvements to the quality of care provided to those who engage in self-harm.

Study protocol for the Multimodal Approach to Preventing Suicide in Schools (MAPSS) project: A regionally based feasibility trial of an integrated response to suicide risk among UK secondary school pupils.

BACKGROUND: Suicide is the leading cause of death of children and young people under 35 in the UK, and suicide rates are rising in this age group. Schools are considered an appropriate and logical setting for youth suicide prevention activities, with universal, selective, and indicated approaches all demonstrating efficacy. Given that international best practice recommends suicide prevention programmes combine these approaches, and that to date this has not been done in school settings in the UK, this study aims to evaluate the feasibility of delivering a suicide prevention programme incorporating universal, selective, and indicated components in UK schools. METHODS: This study is a feasibility cluster-randomised controlled trial (RCT) of an adapted version of the Multimodal Approach to Preventing Suicide in Schools (MAPSS) programme. The programme, initially developed in Australia, involves delivering universal psychoeducation to all pupils, screening them for suicide risk, and delivering Internet-based Cognitive Behavioural Therapy (Reframe IT-UK) to those students identified as being at high-risk for suicide. The programme will be trialled in six secondary schools in Northwest England and will target Year 10 students (14- and 15-year-olds). The primary aims are to assess: 1) the acceptability and safety of delivering MAPSS in a school setting in the UK; 2) the social validity of the MAPSS programme; and 3) the feasibility of delivering a large-scale, appropriately powered, cluster-RCT and economic evaluation of this intervention in the future. Secondary aims are to assess changes over time in mental health and wellbeing outcomes. DISCUSSION: This study is the first to evaluate a suicide prevention programme comprising universal, selective, and indicated components in UK schools. If the programme is found to be feasible, it could be more widely tested in schools and may ultimately lead to reduced rates of suicide and suicidal behaviour in young people.

Youth partnership in suicide prevention research: moving beyond the safety discourse.

OBJECTIVE: In this communication article, we discuss coproduction in suicide prevention research, with an emphasis on involving young people. We critically reflect on the lessons we have learned by working alongside young people, and how these lessons may be useful to other research teams. SUMMARY: The meaningful involvement of young people in the design, implementation and translation of mental health research has received significant attention over the last decade. For most funding bodies, the involvement of patients and the public in the planning and delivery of research is advised and, in many cases, mandatory. When it comes to suicide prevention research, however, things are slightly different in practice. Involvement of young people in suicide prevention research has often been considered a controversial, unfeasible and even risky endeavour. In our experiences of working in this field, such concerns are expressed by funders, Higher Education Health and Safety committees and practitioners. By presenting an example from our research where the involvement of young people as experts by experience was integral, we highlight key lessons learnt that could maximise the potential of youth partnership in suicide prevention research. These lessons take on particular importance in mental health research against the background of long-entrenched power differences and the silencing of service user voices. Professional knowledge, obtained through education and vocational training, has historically taken priority over experiential knowledge obtained through lived experience, in psychiatric practice and research. Although this hierarchy has widely been challenged, any account of coproduction in mental health research is positioned against that background, and the remnants of those inequitable power relationships arguably take on greater resonance in suicide prevention research and require careful consideration to ensure meaningful involvement. CONCLUSION: We conclude that progress in suicide research cannot be fulfilled without the meaningful involvement of, and partnership with, young people with lived experience.

Understanding the processes underlying self-harm ideation and behaviors within LGBTQ+ young people: A qualitative study.

OBJECTIVE: This study aims to understand the processes underlying self-harmful thoughts and behaviors, with and without suicidal intent, among LGBTQ+ young people. METHOD: Nineteen semi-structured interviews took place between October 2019 and May 2020. Participants were aged between 16 and 25 years, had experiences of self-harm ideation and behaviors, and were part of the LGBTQ+ umbrella. A range of sexualities and gender identities were represented: eleven participants were cisgender, six were transgender and two were non-binary. Interviews were transcribed verbatim and anonymised. Thematic analysis and reflective member-checking were used to develop a thematic framework. RESULTS: Three themes were developed from the interviews and evaluated by four participants who engaged with reflective member-checking. Findings indicated that internal processes and external responses to being LGBTQ+ resulted in self-harmful thoughts and behaviors. Alongside these, additional stressors related to being a young person were led to difficulties with self-harm. CONCLUSIONS: Findings from this study indicate that young people often struggle with accepting their LGBTQ+ identity for a number of reasons, whether this is due to access to a resource or their own feelings about their identity. These negative self-perceptions can be enhanced by poor responses from others and additional life stressors which impact their self-esteem or self-perception.HIGHLIGHTSUnderstanding and accepting that one is LGBTQ+ is not always a simple process, struggling with these thoughts can influence self-harm.Lack of LGBTQ+ terminology hinders self-acceptance and caused young people to engage with self-harm.Peers and family members responses to a young people's LGBTQ+ identity is highly significant and can directly led to self-harmful thoughts and experiences.

Which programmes and policies across health and community settings will generate the most significant impacts for youth suicide prevention in Australia and the UK? Protocol for a systems modelling and simulation study.

INTRODUCTION: Suicide is a leading cause of mortality among young people aged 15-24 globally. Despite the deployment of comprehensive suicide prevention strategies, we still do not know which interventions, for which groups of young people, for how long and with what intensity could generate the most significant reductions in suicide rates. System dynamics modelling has the potential to address these gaps. SEYMOUR (System Dynamics Modelling for Suicide Prevention) will develop and evaluate a system dynamics model that will indicate which suicide prevention interventions could generate the most significant reductions in rates of suicide and attempted suicide among young people aged 12-25 in Australia and the UK. METHODS AND ANALYSIS: A comparative case study design, applying participatory system dynamics modelling in North-West Melbourne (Australia) and Birmingham (UK). A computer simulation model of mental health service pathways and suicidal behaviour among young people in North-West Melbourne will be developed through three workshops with expert stakeholder groups (young people with lived experience, carers, clinicians, policy makers, commissioners). The model will be calibrated and validated using national, state and local datasets (inputs). The simulation model will test a series of interventions identified in the workshops for inclusion. Primary model outputs include suicide deaths, self-harm hospitalisations and self-harm presentations to emergency departments. An implementation strategy for the sustainable embedding of promising suicide prevention interventions will be developed. This will be followed by model customisation, re-parameterisation, and validation in Birmingham and adaptation of the implementation strategy. ETHICS AND DISSEMINATION: The project has received approval from the University of Melbourne Human Research Ethics Committee (2022-22885-25971-4), the University of Birmingham Science, Technology, Engineering and Mathematics Ethics Review Committee (ERN_21-02385) and the UK HRA (22/HRA/3826). SEYMOUR's dissemination strategy includes open-access academic publications, conference presentations, accessible findings coproduced with young people, e-briefs to policy makers, webinars for service providers and commissioners.

Smartphones, social Media and Adolescent mental well-being: the impact of school policies Restricting dayTime use-protocol for a natural experimental observational study using mixed methods at secondary schools in England (SMART Schools Study).

INTRODUCTION: Smartphone and social media use is prevalent during adolescence, with high levels of use associated with lower levels of mental well-being. Secondary schools in the UK have introduced policies that restrict daytime use of smartphones and social media, but there is no evaluation on the impact of these policies on adolescent mental well-being. The SMART Schools Study aims to determine the impact of daytime restrictions of smartphone and social media use on indicators of adolescent mental well-being, anxiety, depression, physical activity, sleep, classroom behaviour, attainment and addictive social media use. METHODS AND ANALYSIS: This is a natural experimental observational study using mixed methods. Secondary schools within a 100 mile radius of the recruiting centre in the West Midlands (UK) have been categorised into two groups: Schools that restrict (intervention) and permit (comparator) daytime use of smartphones. We aim to recruit 30 schools (20 restrictive, 10 permissive) and 1170 pupils aged 12-13 and 14-15 years. We will collect data on mental well-being, anxiety and depressive symptoms, phone and social media use, sleep and physical activity from pupil surveys, and accelerometers. Policy implementation measures and data on individual pupil factors will be collected through school staff surveys, and website/policy analysis. Six case study schools will explore individual, school and family/home factors that influence relationships between school smartphone policies, smartphone/social media use, and mental well-being. Economic evaluation will be completed through a cost-consequence analysis from an education sector perspective. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Birmingham's Research Ethics Committee (ERN_22-0723). Parents/carers of pupil participants can complete a form to opt their child out of the study. Pupil, school staff and parent/carer participants are asked to complete online/written consent (or assent). Findings will be disseminated through policy briefings, resources for schools, social media, reports, and open access publications. TRIAL REGISTRATION NUMBER: ISRCTN77948572.

A prospective study of PTSD following recovery from first-episode psychosis: the threat from persecutors, voices, and patienthood.

OBJECTIVES: Approximately one third of people with early psychosis report post-traumatic symptoms, some of which are thought to arise from traumatic experiences associated with psychosis itself. This prospective study tested hypotheses based on retrospective findings that threat appraisals of voices, persecutors, or the new label of 'mental health patient' predict symptoms of post-traumatic stress disorder (PTSD). METHODS: Appraisals of power and threat from voices and other persecutors and appraisals of the threat posed to identity by the diagnosis were assessed during the first acute phase of psychosis. Eighteen months later, PTSD symptom levels and diagnosis were established. DESIGN: Prospective. RESULTS: Of 39 participants who completed the follow-up phase, 12 (31%) met criteria for PTSD diagnosis. Nineteen (49%) of the participants were still distressed by memories of their psychosis or the associated treatment. During the acute phase of psychosis, appraisals of threat from voices and persecutors were strongly associated with distress. With the exception of the perceived ability to cope with threat, none of these appraisals were predictive of subsequent post-traumatic stress however. Similarly, only one appraisal of the diagnosis (loss of control) was predictive of PTSD. CONCLUSION: It may be that retrospective studies have overestimated the influence of candidate appraisals in predicting PTSD. It might also be that assessments made during the acute phase of psychosis preceded a key phase of psychological processing that takes place during the immediate aftermath of the psychotic episode. A staged prospective design is required to uncover the true impact of psychosis on PTSD.

Supporting general practitioners in the assessment and management of suicide risk in young people: an evaluation of an educational resource in primary care.

AIM: To conduct a local evaluation of the use of the educational resource: Suicide in Children and Young People: Tips for GPs, in practice and its impact on General Practitioners (GPs)' clinical decision making. BACKGROUND: This Royal College of General Practitioners (RCGP) resource was developed to support GPs in the assessment and management of suicide risk in young people. METHOD: The dissemination of the educational resource took place over a nine month period (February 2018-October 2018) across two Clinical Commissioning Groups in West Midlands. Subsequently, a survey questionnaire on GPs' experiences of using the resource was sent to GPs in both Clinical Commissioning Groups (CCGs). FINDINGS: Sixty-two GPs completed the survey: 21% reported that they had used the resource; most commonly for: (1) information; (2) assessing a young person; and (3) signposting themselves and young people to relevant resources. Five out of thirteen GPs (38.5%), who responded to the question about whether the resource had an impact on their clinical decision making, reported that it did; four (30.7%) responded that it did not; and four (30.7%) did not answer this question. Twenty out of thirty-two GPs (62.5%) agreed that suicide prevention training should be part of their NHS revalidation cycle. The generalizability of the findings is limited by the small sample size and possible response and social desirability bias. The survey questionnaire was not validated. Despite the limitations, this work can be useful in informing a future large-scale evaluation of the RCGP online resource to identify barriers and facilitators to its implementation.

Feasibility and acceptability of experience sampling among LGBTQ+ young people with self-harmful thoughts and behaviours.

This study was the first to determine whether it was feasible and acceptable to use experience sampling methods (ESM) among LGBTQ+ young people, who had current experiences of self-harm. Sixteen LGBTQ+ young people (16-25 years old) took part in the experience sampling study. This included a baseline assessment, a 7-day ESM assessment (participants were sampled six times a day using a phone app), and the option of an interview at the end of the 7-day ESM assessment. Feasibility data was descriptively analysed, with pilot ESM data presented. Qualitative data was thematically analysed to determine the acceptability (barriers and facilitators) of taking part in this study. Study feasibility was assessed by enrolment rate (55.2%), participant retention across assessment period (100%), ESM app feasibility (87.5%), and good adherence to total number of ESM surveys (67.6%). Individual study adherence ranged between 43 and 95.2%. Study acceptability was assessed by participant interviews. Thematic analysis indicated four superordinate themes; (i) Self-reflection and awareness; (ii) Practicalities of ESM surveys; (iii) Daily timeframes; and (iv) Suggestions for future studies. Pilot ESM data demonstrates that there was fluctuation of depressive and anxiety symptoms within- and between- participants over the course of the study, however, greater sample power is needed for full analysis. This study demonstrated that ESM designs are feasible and acceptable among LGBTQ+ young people with current experiences of self-harm. Pilot data indicated that specific experiences and moods are likely to be important to self-harm. These potentially have a temporal influence on self-harm behaviour or ideation, and therefore should be examined in a fully powered sample.

Characterization of the nicotinic acetylcholine receptor antibodies after an unexpected increase of antibody titer in thymoma associated myasthenia gravis patients.

Two thymoma-associated myasthenia gravis patients with chronic well-controlled disease but an unexpected increase in anti-nAChR autoantibodies titer are reported. The specificity of anti-nAChR autoantibodies directed against extracellular parts of the receptor was studied in order to investigate the discrepancy between clinical and immunological status. Analysis of the anti-nAChR autoantibodies recognizing the extracellular parts of the nAChR revealed that when the concentration of anti-nAChR autoantibodies titer increased both patients had non-anti-α1 autoantibodies. Since the clinical profile of both patients remained unchanged, the increase of non-anti-α1 autoantibodies did not affect the 2 patients' disease progression. Thus, immunotherapy modification due to an increase of anti-nAChR autoantibodies titer could be erroneous and potentially harmful.

Assessing and Responding to Suicide Risk in Children and Young People: Understanding Views and Experiences of Helpline Staff.

INTRODUCTION: Suicide is a key issue impacting children and young people. Helplines offer unique benefits, such as anonymity, varied communication avenues and low cost, which help to promote help-seeking behaviour. The aim of this study was to explore the views and experiences of helpline organisations of identifying, assessing, and managing suicide risk among children and young people. METHODS: Thirteen professionals from three UK-based helplines and online counselling services took part in semi-structured interviews between November 2020 and January 2021 via Zoom. Interviews were transcribed verbatim and analysed using Thematic Analysis. RESULTS: Three superordinate themes were identified: (i) Starting conversations about suicide; (ii) Identifying and responding to "imminent" suicide risk; and (iii) Responses to suicide risk in relation to safeguarding. LIMITATIONS: Recruitment was limited by COVID-19 due to the demands needed from helplines at this time. CONCLUSIONS: Our findings highlight not only the different types and range of services helpline organisations offer to young people who might be at risk of suicide, but most importantly the distinct role they have in young people's help-seeking pathway.

The effectiveness of gaming interventions for depression and anxiety in young people: systematic review and meta-analysis.

BACKGROUND: Recent research has investigated the use of serious games as a form of therapeutic intervention for depression and anxiety in young people. AIMS: To conduct a systematic review and meta-analysis into the effectiveness of gaming interventions for treating either depression or anxiety in individuals aged 12-25 years. METHOD: An electronic search was conducted on the 30 March 2020, using PsycINFO, ISI Web of Science Core Collection, Medline and EMBASE databases. Standardised effect sizes (Hedge's g) were calculated for between-participant comparisons between experimental (therapeutic intervention) and control conditions, and within-participant comparisons between pre- and post-intervention time points for repeated measures designs. RESULTS: Twelve studies (seven randomised controlled trials (RCTs) and five non-randomised studies) were included. For RCTs, there was a statistically significant and robust effect (g = -0.54, 95% CI -1.00 to -0.08) favouring the therapeutic intervention when treating youth depression. For non-RCTs, using a repeated measures design, the overall effect was also strong (g = -0.75, 95% CI -1.64 to 0.14) favouring therapeutic intervention, but this was not statistically significant. Interestingly, we found no statistically significant effect for treating youth anxiety. CONCLUSIONS: There is preliminary evidence to suggest that gaming interventions are an effective treatment for youth depression, but not anxiety. Further research is warranted to establish the utility, acceptability and effectiveness of gaming interventions in treating mental health problems in young people.

Analysis of nAChR Autoantibodies Against Extracellular Epitopes in MG Patients.

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies targeting components of the postsynaptic membrane of the neuromuscular junction (NMJ), leading to neuromuscular transmission deficiency. In the vast majority of patients, these autoantibodies target the nicotinic acetylcholine receptor (nAChR), a heteropentameric ion channel anchored to the postsynaptic membrane of the NMJ. Autoantibodies in patients with MG may target all the subunits of the receptor at both their extracellular and intracellular regions. Here, we combine immunoadsorption with a cell-based assay to examine the specificity of the patients' autoantibodies against the extracellular part of the nAChR. Our results reveal that these autoantibodies can be divided into distinct groups, based on their target, with probably different impacts on disease severity. Although our findings are based on a small sample group of patients, they strongly support that additional analysis of the specificity of the autoantibodies of patients with MG could serve as a valuable tool for the clinicians' decision on the treatment strategy to be followed.