Bcl-2 supports survival and metabolic fitness of quiescent tissue-resident ILC3.

Group 3 innate lymphoid cells (ILC3) are potent effector cells with critical roles in enforcing immunity, barrier integrity and tissue homeostasis along the gastrointestinal tract. ILC3 are considered primarily tissue-resident cells, seeding the gastrointestinal tract during embryonic stages and early life. However, the mechanisms through which mature ILC3 are maintained within adult tissues are poorly understood. Here, we report that lymphoid tissue-inducer-like (LTi-like) ILC3 exhibit minimal turnover in the healthy adult intestinal tract, persist for extended periods of time, and display a quiescent phenotype. Strikingly, during enteric bacterial infection LTi-like ILC3 also exhibit negligible hematopoietic replenishment and remain non-proliferative, despite robustly producing cytokines. Survival of LTi-like ILC3 was found to be dependent upon the balance between the metabolic activity required to drive effector function and anti-apoptotic programs. Notably, the pro-survival protein B-cell lymphoma-2 (Bcl-2) was required for the survival of LTi-like ILC3 ex vivo but was rendered partially dispensable if mitochondrial respiration was inhibited. Together we demonstrate LTi-like ILC3 are a tissue-resident, quiescent population that persist independently of hematopoietic replenishment to survive within the intestinal microenvironment.

Refugees' and asylum seekers' experiences of individual psychological therapy: A qualitative meta-synthesis.

PURPOSE: The current review aimed to synthesise qualitative literature exploring adult refugees' and asylum seekers' experiences of individual psychological therapy. METHODS: A comprehensive systematic search of the following databases led to the identification of eight studies for inclusion in this review: PsycINFO, PsycARTICLES, MEDLINE, EMBASE, CINAHL and Academic Search Ultimate. All selected studies used qualitative methodology to explore refugees' and asylum seekers' experiences of individual psychological therapy. Studies were appraised using an adapted version of the Critical Appraisal Skills Programme (CASP) Tool. The data from these selected studies were then synthesised using a meta-ethnographic approach. RESULTS: The synthesis of selected studies resulted in the development of five themes; (i) the importance of recognition and validation within therapy, (ii) building a human connection within the therapeutic relationship and the importance of cultural competency, (iii) revisiting trauma, managing difficult emotions from therapy and regaining hope, (iv) the value of practical interventions, (v) 'one should not wake up the djinns (demons)'-cultural stigma and accessing therapy. These themes illustrated the complexities of working therapeutically with asylum seekers and refugees and the vital role of building trust and safety within the therapeutic relationship prior to engagement in therapeutic work. The results also highlighted varied responses to engaging in trauma work ranging from participants finding the experience transformative to others finding it unhelpful, some participants preferred more practical interventions. Participants' cultural backgrounds and pre-conceptions around therapy impacted on engagement and the therapist's cultural competency was a significant factor in therapeutic engagement. CONCLUSIONS: Working therapeutically with asylum seekers and refugees involves a number of factors for consideration. Forced migrants' socio-political context was seen as central to their experiences of distress and recognition of these factors was imperative for positive therapeutic engagement. This review highlights a number of clinical implications to guide practitioners working therapeutically with this community.

Group 2 Innate Lymphoid Cells Are Detrimental to the Control of Infection with Francisella tularensis.

Innate lymphoid cells (ILCs) are capable of rapid response to a wide variety of immune challenges, including various respiratory pathogens. Despite this, their role in the immune response against the lethal intracellular bacterium Francisella tularensis is not yet known. In this study, we demonstrate that infection of the airways with F. tularensis results in a significant reduction in lung type 2 ILCs (ILC2s) in mice. Conversely, the expansion of ILC2s via treatment with the cytokine IL-33, or by adoptive transfer of ILC2s, resulted in significantly enhanced bacterial burdens in the lung, liver, and spleen, suggesting that ILC2s may favor severe infection. Indeed, specific reduction of ILC2s in a transgenic mouse model results in a reduction in lung bacterial burden. Using an in vitro culture system, we show that IFN-γ from the live vaccine strain-infected lung reduces ILC2 numbers, suggesting that this cytokine in the lung environment is mechanistically important in reducing ILC2 numbers during infection. Finally, we show Ab-mediated blockade of IL-5, of which ILC2s are a major innate source, reduces bacterial burden postinfection, suggesting that IL-5 production by ILC2s may play a role in limiting protective immunity. Thus, overall, we highlight a negative role for ILC2s in the control of infection with F. tularensis. Our work therefore highlights the role of ILC2s in determining the severity of potentially fatal airway infections and raises the possibility of interventions targeting innate immunity during infection with F. tularensis to benefit the host.

Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses.

Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens-including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 are found to be uniquely preprimed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine-producing capacity of ILC2. Mechanistically, amino acid uptake determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.

A Good Day for Helminths: how parasite-derived GDH suppresses inflammatory responses.

Parasitic helminths are often associated with immunoregulation, which allows them to survive in their hosts in the face of type 2 immune responses. They achieve this feat through the secretion of multiple immunomodulatory factors. In this issue of EMBO Reports, Prodjinotho et al show that the parasitic cestode Taenia solium induces regulatory T-cell responses in mice and humans through the release of the metabolic enzyme Glutamate dehydrogenase (GDH), which may be a conserved pathway of immunoregulation in many helminths (Prodjinotho et al, 2022).

Becoming a mother in the context of sex work: Women's experiences of bonding with their children.

Many females engaged in sex work are mothers, often experiencing poverty, violence, marginalization, and psychological distress, factors also found to affect parental bonds. However, little is known about how this context impacts the bonding process. Given the ubiquity of sex work across geographical territories, understanding the relationship it has with mother-child bonding is an important international consideration in providing healthcare for sex working mothers and their children. Therefore, in this study we sought to explore women's experiences of bonding with their children in the context of sex work. We interviewed six women in the UK who were sex working during the first two years of their child's life about their bonding experiences and analyzed transcripts using Interpretative Phenomenological Analysis. We identified four themes were identified: (1) the complex process of bonding; (2) the role of powerlessness on bonding; (3) the powerful impact of receiving help, and (4) new perspectives of the body and sex work following motherhood. Findings contribute to the research literature on bonding by emphasizing the value of supportive care and the importance of social context, indicating specific factors to inform psychological support among sex working women.

Experiences of Compassion in Adults With a Diagnosis of Borderline Personality Disorder: An Interpretative Phenomenological Analysis.

The study explored experiences of compassion in adults with a diagnosis of Borderline Personality Disorder (BPD) to further the development of the construct of compassion in relation to BPD. Interpretative Phenomenological Analysis was used to develop themes from the narratives of six adults with a diagnosis of BPD. Five themes emerged: Emotional Connection to Suffering, Empathic Understanding, Prioritisation of Needs, A Model of Genuine Compassion and Developing Acceptance and Worth. Participants described the role of compassion in their difficulties, including the adverse impact of experiences of incompassion upon their sense of self. The themes were integrated into a model that highlighted a process of recovery through therapeutic encounters with others in which genuine compassion was modelled. In addition, barriers to compassion and factors facilitating the development of compassion emerged from the analysis and have implications for clinical practice.

Twitchy, the Drosophila orthologue of the ciliary gating protein FBF1/dyf-19, is required for coordinated locomotion and male fertility.

Primary cilia are compartmentalised from the rest of the cell by a ciliary gate comprising transition fibres and a transition zone. The ciliary gate allows the selective import and export of molecules such as transmembrane receptors and transport proteins. These are required for the assembly of the cilium, its function as a sensory and signalling centre and to maintain its distinctive composition. Certain motile cilia can also form within the cytosol as exemplified by human and Drosophila sperm. The role of transition fibre proteins has not been well described in the cytoplasmic cilia. Drosophila have both compartmentalised primary cilia, in sensory neurons, and sperm flagella that form within the cytosol. Here, we describe phenotypes for twitchy the Drosophila orthologue of a transition fibre protein, mammalian FBF1/C. elegans dyf-19. Loss-of-function mutants in twitchy are adult lethal and display a severely uncoordinated phenotype. Twitchy flies are too uncoordinated to mate but RNAi-mediated loss of twitchy specifically within the male germline results in coordinated but infertile adults. Examination of sperm from twitchy RNAi-knockdown flies shows that the flagellar axoneme forms, elongates and is post-translationally modified by polyglycylation but the production of motile sperm is impaired. These results indicate that twitchy is required for the function of both sensory cilia that are compartmentalised from the rest of the cell and sperm flagella that are formed within the cytosol of the cell. Twitchy is therefore likely to function as part of a molecular gate in sensory neurons but may have a distinct function in sperm cells.

How Individuals Who Self-Harm Manage Their Own Risk-'I Cope Because I Self-Harm, and I Can Cope with my Self-Harm'.

Self-harm is a complex and idiosyncratic behaviour. This article focuses on how those who self-harm manage their own risk. Utilising opportunity sampling, ten members of a self-harm support group were interviewed about how they risk manage their self-harm and the data analysed using interpretative phenomenological analysis. The analysis showed that all participants were actively involved in risk management of their self-harm. Through a process of managing consequences, exercising control in the process, and an awareness of the social context. It is posited that people who self-harm should be viewed as actively engaging with the risks of self-harm whilst it is a coping mechanism, as opposed to passive or ignoring. This understanding can be integrated into current risk management plans within services and invites a more dynamic conversation of self-harm between services users and services. Effective risk management involves good relationships between individuals who self-harm and clinicians, services which promote positive risk taking as opposed to defensive practice, and true collaboration between services and service users.

A qualitative exploration of how people with bipolar disorder consider risk-taking in everyday decisions.

BACKGROUND: Difficulties with decision making and risk taking in individuals with bipolar disorder (BD) have been associated with mood episodes. However, there is limited information about these experiences during euthymia, the mood state where people with BD spent the majority of their time. AIMS: To examine how individuals with BD consider risk in everyday decisions during their euthymic phase. METHOD: We conducted a qualitative study that used semi-structured audio recorded interviews. Eight euthymic participants with confirmed BD were interviewed, and we used interpretative phenomenological analysis to analyse the data. RESULTS: We identified four themes. The first theme, 'Who I really am', involves the relationship between individual identity and risks taken. The second theme, 'Taking back control of my life', explored the relationship between risks taken as participants strove to keep control of their lives. The third theme, 'Fear of the "what ifs"', represents how the fear of negative consequences from taking risks impacts risk decisions. Finally, the fourth theme, 'The role of family and friends', highlights the important role that a supporting network can play in their lives in the context of taking risks. CONCLUSIONS: The study highlights aspects that can impact on an individual with BD's consideration of risk during euthymia. Identity, control, fear and support all play a role when a person considers risk in their decision-making process, and they should be taken into consideration when exploring risk with individuals with BD in clinical settings, and inform the design of future interventions.

The quest for genuine care: A qualitative study of the experiences of young people who self-harm in residential care.

Levels of self-harm for young people in care are high, and even higher for those in residential care. Recent research highlights the importance of understanding self-harm relationally. Such an approach may be of particular value for understanding the self-harm of young people in care. The aim of this research was to understand the experiences of young people who self-harm whilst living in residential care, with a particular focus on the effect of the care setting on their self-harm. Five young people participated in semi-structured interviews which were analysed using Interpretive Phenomenological Analysis. Four themes emerged: 'The black hole of self-harm', 'Seeking genuine care and containment', 'The cry to be understood' and 'Loss of control to the system.' Young people recognised their need for support with their self-harm, but organisationally driven approaches to managing risk contributed to a perception that the care offered was not genuine, which led to an unwillingness to accept care. The findings highlight the need for a more compassionate, relational response to young people who self-harm in residential care.

What is the process by which a decision to administer electroconvulsive therapy (ECT) or not is made? A grounded theory informed study of the multi-disciplinary professionals involved.

PURPOSE: To develop a grounded theory-informed model explaining the decision-making process professionals in multi-disciplinary teams go through in deciding whether to administer electroconvulsive therapy (ECT) or not. METHODS: A grounded theory informed methodology was used to analyse the data offered by ten participants who had all been involved in the process of deciding if someone has ECT or not. RESULTS: The core categories, described as 'layers' in this research, 'personal and professional identity'; 'subjective vs objective'; 'Guidelines or Clinical Instinct?'; 'Someone has to take Responsibility' and 'the decision in action', were constructed from the data. CONCLUSIONS: The study describes a useful insight into the layers of the decision-making process that could be further considered in clinical settings. The model highlights the decision to give ECT that has many different layers including professional identity, how a person understands the evidence base, past experiences, and the amount of power they have in the process. The consultant psychiatrist and the patient were seen as holding most power in the process depending on whether the Mental Capacity Act (2005) or Mental Health Act (2007) was being followed. Patients were seen to experience a very different decision-making process dependant on the personal views of the professionals in relation to ECT.

Orchestration of intestinal homeostasis and tolerance by group 3 innate lymphoid cells.

The gastrointestinal tract is the primary site of exposure to a multitude of microbial, environmental, and dietary challenges. As a result, immune responses in the intestine need to be tightly regulated in order to prevent inappropriate inflammatory responses to exogenous stimuli. Intestinal homeostasis and tolerance are mediated through a multitude of immune mechanisms that act to reinforce barrier integrity, maintain the segregation and balance of commensal microbes, and ensure tissue health and regeneration. Here, we discuss the role of group 3 innate lymphoid cells (ILC3) as key regulators of intestinal health and highlight how increasing evidence implicates dysregulation of this innate immune cell population in the onset or progression of a broad range of clinically relevant pathologies. Finally, we discuss how the next generation of immunotherapeutics may be utilized to target ILC3 in disease and restore gastrointestinal tolerance and tissue health.

Understanding experiences of the self-harm of others: A qualitative exploration of the views of young people with complex mental health needs.

As adolescent self-harm is a growing public health concern, more research is needed to identify potential risk factors. Studies have highlighted that exposure to the self-harm of others may be a risk factor associated with engagement in self-harm. However, research investigating young people's experiences of the self-harm of others has been limited. This qualitative study aimed to explore young people's experiences of the self-harm of others and interviewed a total of eight young people (five females and three males; aged between 13 and 18 years) resident at one of two adolescent mental health inpatient units in the North of England. The interviews were analysed using Interpretative Phenomenological Analysis and four themes were identified: 'Pre-admission exposure to self-harm', 'Exposure on the inside: An unpleasant environment', 'Helper vs helped' and 'Separation from the attention seekers: competing for authenticity'. Prevention efforts to reduce the social transmission and stigma surrounding self-harm among young people are discussed.

A qualitative study exploring the effects of attending a community pain service choir on wellbeing in people who experience chronic pain.

In line with growing evidence of the health benefits of singing, this study aimed to explore participants' perceptions of the impact of a service-user-led community pain choir on their psychological wellbeing, self-efficacy and relationships with their chronic pain. The choir has links to a multidisciplinary pain management service, which is informed by the ethos of solution-focused (SF) principles, specifically in identifying and drawing upon patients' resources. Seven choir members participated in semi-structured interviews, grounded in lines of enquiry commonly used in SF practice. Thematic analysis of the data uncovered seven themes: Physical Improvements, Emotional Impact, Personal Growth, Interpersonal Processes, Relationship with the 'Self', Living Well with Pain and Sharing the Music and Spreading the Word. Participants' narratives provided support for participation in the choir in enhancing positive affect, self-worth, interpersonal relationships and overall wellbeing. The choir enabled continued progress towards accomplishing key pain management programme aims: self-management, coping and living well with pain. Findings expanded upon existing evidence relating to singing and wellbeing by highlighting the choir's role in promoting resilience and acceptance of pain. Clinical implications are explored in relation to psychosocial dimensions of pain.

Exploring the Role of Mental Imagery in the Experience of Self-injury: An Interpretative Phenomenological Analysis.

BACKGROUND: Research has implicated causal, mediating and meaningful roles for mental imagery in the experience of psychological distress, including self-injury. AIMS: The present study aimed to further the understanding of this relationship through exploring the lived experiences of mental imagery from the perspective of those who self-injure. METHOD: This study employed an inductive qualitative design using semi-structured interviews and Interpretative Phenomenological Analysis (IPA). Ten participants were recruited from universities in North West England. RESULTS: Three main themes were identified from the analysis: (i) The origins and precipitants of self-injurious imagery; (ii) What it is like to experience self-injurious imagery; and (iii) The meaning and interpretation of self-injurious imagery. CONCLUSIONS: The study findings indicate that mental imagery is an important experience for those who self-injure. Clinical and research implications of the findings are discussed.

Resilience and vision impairment in older people.

Some people fare better than others when faced with adversity; they appear to be more 'resilient'. This article explores the concept of resilience in the context of vision impairment using two linked sets of narrative interview data from 2007 to 2010. Three case studies were analysed in detail using a framework approach based upon a social-ecological model of resilience and vision impairment. Within the model a range of assets and resources are identified which influence an individual's capacity for resilience. A set of criteria were used to establish the extent to which each individual appeared to be resilient at each point in time. Analysis revealed that it is not merely the presence or absence of individual, social, and community resources - but how these resources interact with each other - that influences resilience and can create a risk to wellbeing. To possess only some of these resources is not sufficient; there is a co-dependency between these resources which requires the presence of other resources for resilience to be achieved. Resilience is not a fixed state; individuals can become more or less resilient as their circumstances and resources change over time. We suggest that the concept of resilience has much to offer the field of vision impairment as it allows the identification of enablers as well as areas of barriers to improving people's health and wellbeing and suggests further opportunities for service providers to engage with clients, even those who appear to be supported, as people's social, economic and emotional landscapes continue to change over time, rather than identifying deficit.

Quantitative findings from a mixed methods evaluation of once-weekly therapeutic community day services for people with personality disorder.

BACKGROUND: Quantitative findings are presented from a mixed methods study of four one-day-a-week therapeutic communities for people with personality disorder (qualitative findings from the same study are reported in a separate paper). The evaluation assessed both the clinical efficacy of the model and its acceptability to service users, service employees and those who refer clients to the services. AIMS: The study aimed to clarify whether one-day therapeutic communities can be effective for people with personality disorder. METHOD: Changes in the functioning of service users who attended the day services were assessed every 12 weeks for up to 1 year. RESULTS: We found significant improvements in both the mental health and social functioning of service users. Changes in patterns of self-harm and service use were suggestive of possible underlying improvements but failed to reach significance levels. We also found evidence of the possible offset of costs within 16 months of an individual leaving one of the services. CONCLUSIONS: This study suggests one-day therapeutic communities may be both clinically- and cost-effective for people with personality disorder.

Qualitative findings from a mixed methods evaluation of once-weekly therapeutic community day services for people with personality disorder.

BACKGROUND: This paper presents qualitative findings from a mixed methods study of four one-day-a-week therapeutic communities (TCs) in the north of England for people with personality disorder. Quantitative findings from the study are presented separately. AIMS: The study aimed to ascertain whether one-day-a-week TCs can be effective in addressing the problems associated with personality disorder. METHOD: The qualitative component of the study comprised semi-structured interviews with service users, service user consultants, staff and referrers. This paper reports findings from the interviews with service users. FINDINGS: The qualitative findings indicate underlying changes in thinking that may account for some of the measurable changes in members' mental health and functioning reported in the quantitative findings. In particular, the services enable individuals to address two main problem areas: relating to others and self-harm. CONCLUSIONS: The study suggests that once-weekly TCs provide an effective therapeutic approach to the problems associated with personality disorder.

User involvement in the construction of a mental health charter: an exercise in communicative rationality?

BACKGROUND: This paper uses Jürgen Habermas's Theory of Communicative Action as a lens through which to examine the development of a local mental health charter. OBJECTIVE: To assess whether the Charter represents the product of a communicatively rational process. RESEARCH DESIGN AND SETTING: The paper is based on an analysis of the text of the Charter, and on documentation relating to its development, including notes of discussion groups used to identify its themes. FINDINGS: An analysis of the notes of the discussion groups against the text of the Charter shows that the Charter's themes are based broadly on the views generated in the discussion groups. However, they also draw on norms derived from wider discourses not reflected in the discussion groups, and exclude other specific local issues. The strength of feeling expressed in the discussion groups is also toned down in the language of the Charter. DISCUSSION: The development of the Charter was based on a participatory process that can be said to have contained elements of both communicative and strategic rationality. The strategic rationality involved in translating service users' views into language that would be acceptable to those working in the system can be seen as necessary for the Charter to succeed in bringing about change. In drawing also on communicatively generated norms from the wider public sphere the Charter can be seen as reflecting a form of generalized communicative rationality. CONCLUSION: The Charter represents a 'sluice' by which communicative rationality is drawn into the mental health system.