Understanding the Factors That Contribute to Creating a Collaborative Psychological Formulation: A Qualitative Systematic Review.

OBJECTIVES: Creating a formulation is one of the key competencies of a clinical psychologist and is understood to be important for guiding therapeutic input and understanding client distress. However, client experience of formulations can vary, with some reporting it is unhelpful and distressing. This novel review explores the experiences of clinicians and clients when creating a formulation, specifically the barriers and facilitators to collaborating on a formulation. This ultimately aims to improve client experience and engagement in formulation. METHODS: A systematic search of PubMed, Web of Science, PsycINFO and EMBASE was conducted using PRISMA guidelines. The protocol was registered on PROSPERO. This search was conducted using terms related to 'psychological formulation' and 'experience'. Nineteen qualitative papers met inclusion criteria and were appraised using the Critical Appraisal Skills Programme. Findings that pertained to formulation were thematically synthesised. RESULTS: Three analytical themes were identified: toleration of the formulation process-'a necessary evil', which highlights the potential emotional impact of formulation on the client and indicates the importance of responding to client readiness and expectations of formulation; development of the therapeutic relationship-'it's like a two way thing, isn't it?', which suggests that client empowerment, adapting to client needs and clinicians creating a safe and containing environment facilitated the formulation process; systemic factors-'walking a tightrope', which highlights the constraints of resources and team dynamics in therapists' ability to engage in collaborative formulation. CONCLUSION: Facilitators to a collaborative formulation include the following: simple formulations, thorough assessment and preparation for formulation, 'doing with' activities such as timelines and diagrams and working environments that include supportive colleagues and time for reflection and training.

The revised Psychosis Attachment Measure: further psychometric evidence.

PURPOSE: Disorganised attachment is a key concept in understanding the development of psychosis. However, existing questionnaires of adult attachment do not adequately measure this construct hindering future research into the psychosocial causes of psychosis. The most widely measure of adult attachment in people experiencing psychosis is the Psychosis Attachment Measure (PAM). The measure has recently been revised to include disorganised attachment items. This study develops previous research by providing a rigorous examination the psychometric properties of the revised questionnaire (PAM-R). METHODS: A total of 407 participants with self-reported experiences of psychosis completed a battery of questionnaires which included the PAM-R and other measures which were conceptually related to the concept of disorganised attachment. RESULTS: Confirmatory factor analysis (CFA) indicated a three-factor solution with factors corresponding to anxious, avoidant, and disorganised attachment. The majority of the fit statistics were acceptable with the exception of the RMSEA statistic. Internal consistency and test-retest reliability were good for all subscales. The disorganised subscale correlated in expected directions with other measures of attachment, dissociation, trauma, and psychotic experiences. CONCLUSION: The PAM-R is a valid and reliable measure of adult attachment. It is a practical assessment tool for clinicians and researchers to measure insecure and disorganised attachment patterns that is acceptable to people experiencing psychosis.

The key components of a clinical psychology formulation: A consensus study.

OBJECTIVE: Psychological formulation is a key competency for clinical psychologists. However, there is a lack of consensus regarding the key components and processes of formulation that are hypothesized to contribute to poor reliability of formulations. The aim of this study was to develop consensus on the essential components of a formulation to inform training for clinical psychologists and best practice guidelines. METHODS: A Delphi methodology was used. Items were generated from the literature and discussed and refined with a panel of experts (n = 10). In round one, 110 clinical psychologists in the United Kingdom rated the importance of components of formulation via an online questionnaire. Criteria for consensus were applied and statements were rerated in round two if consensus was not achieved. RESULTS: Consensus was achieved on 30 items, with 18 statements regarding components of a formulation and 12 statements regarding formulation process. Items that clinicians agreed upon emphasized the importance of integrating sociocultural, biological, strengths and personal meaning alongside well-established theoretical frameworks. Consensus was not reached on 20 items, including whether a formulation should be parsimonious or adhere to a model. CONCLUSION: Our findings provide mixed evidence regarding consensus on the key components of formulation. There was an agreement that formulation should be client-led and incorporate strengths and sociocultural factors. Further research should explore client perspectives on the key components of formulation and how these compare to the clinicians' perspectives.

Experiences of a communication-skills course for care partners of people living with dementia, empowered conversations: A qualitative framework analysis.

OBJECTIVES: Our aims were to examine whether an experiential course for care partners of people living with dementia, Empowered Conversations (EC), was acceptable to participants and to explore participants' perceptions of the impact of the course upon their communicative interactions. EC is based on an integrative model derived from psychological and linguistic theory and empirical evidence. EC is based on mentalisation theory, perceptual control theory and linguistic theory (The Communicative Impact Model). METHODS: Qualitative data were collected via 28 semistructured interviews. Framework analysis was used to analyse data. RESULTS: Three superordinate themes, 'improved communication', 'improved well-being' and 'support through others' were identified. Twenty-seven out of the 28 participants described feeling that they were able to better connect with the person living with dementia that they were supporting through attending EC. CONCLUSIONS: The findings indicated that EC was acceptable and beneficial to care partners. Care partners developed a range of strategies and understandings that enabled them to communicate better with the person they were supporting, enhanced well-being and relationships, as well as developing social networks. This is the first qualitative study to examine a psychosocial intervention for care partners of people living with dementia using a non-CBT framework and indicates that perceived control could influence how care partners respond to stress and difficulties.

Protocol of a feasibility randomised controlled trial of Empowered Conversations: training family carers to enhance their relationships and communication with people living with dementia.

Background: Communication difficulties can cause frustration, low mood, and stress for people living with dementia and their carer. Carers should be offered training on adapting their communication skills. However, it is not common for skills-based education to examine emotional aspects of care and the effect of dementia on relationships. The Empowered Conversations (EC) training course was developed in response to a gap in service provision and has been adapted to a virtual format (Zoom). It addresses the specific psychological, relationship, and communication needs of informal and family dementia carers. The primary aim of the study is to investigate the feasibility of conducting a multi-centre randomised controlled evaluation trial of EC. Secondary aims include exploring the acceptability of delivering the intervention online and examining the optimum way of establishing cost-effectiveness. Methods: The feasibility trial uses a pragmatic data-collector blind parallel two-group RCT design with two arms (EC intervention plus treatment as usual, and treatment as usual waitlist control). There will be a 2:1 allocation in favour of the EC-training intervention arm. 75 participants will complete baseline outcome measures exploring their role as a carer, including their physical and mental health, attitudes to caring, quality of life, and use of health and social care services. These will be repeated after six-months. Participants allocated to the treatment group who complete the course will be invited to participate in a qualitative interview discussing their experience of EC. Conclusions: The study will investigate recruitment pathways (including facilitators and barriers to recruitment), estimate retention levels and response rates to questionnaires, obtain additional evidence regarding proof of concept, and consider the most appropriate primary outcome measures and methods for evaluating cost-effectiveness. The results of the feasibility study will be used to inform the development of a multicentre randomised controlled trial in the United Kingdom. Registration: ISRCTN15261686 (02/03/2022).

There are 700,000 family and informal carers for people living with dementia in the UK alone. Sixty-four percent of informal carers in England say they have limited support for the range of psychological and social needs they experience. It can be difficult to keep communicating well due to thinking and memory changes that caused by dementia. This can lead to frustration, low-mood and stress for both people living with dementia and their carers. The 6-session online Empowered Conversations course is designed to enable carers to maintain and improve good communication and relationships with those they support. Course facilitators are trained to provide specific communication techniques, ways of managing conflicts, and working with difficult emotions. The course has been tried out over the last 4-years and changes made. Feedback from informal carers indicates it is in an optimum form and we are ready to test it further in a large trial. Before this is done, it is necessary to complete a smaller 'feasibility' trial to check whether such a larger trial is possible. This article explains how the feasibility trial will be carried out. Our 'feasibility' trial will check several things. We want to make sure that carers would be willing to have an only 66% chance of receiving the course straight away, because it is essential to have a comparison group. The remaining 33% of carers would be offered the course 6-months later. We want to ensure that our design is good enough to identify any improvement in carers' well-being, relationships and communication. We will also ask carers to take part in a one-to-one interview about their experiences of the course, including their views on the course being delivered on Zoom.

Nanoscaled RIM clustering at presynaptic active zones revealed by endogenous tagging.

Chemical synaptic transmission involves neurotransmitter release from presynaptic active zones (AZs). The AZ protein Rab-3-interacting molecule (RIM) is important for normal Ca2+-triggered release. However, its precise localization within AZs of the glutamatergic neuromuscular junctions of Drosophila melanogaster remains elusive. We used CRISPR/Cas9-assisted genome engineering of the rim locus to incorporate small epitope tags for targeted super-resolution imaging. A V5-tag, derived from simian virus 5, and an HA-tag, derived from human influenza virus, were N-terminally fused to the RIM Zinc finger. Whereas both variants are expressed in co-localization with the core AZ scaffold Bruchpilot, electrophysiological characterization reveals that AP-evoked synaptic release is disturbed in rimV5-Znf but not in rimHA-Znf In addition, rimHA-Znf synapses show intact presynaptic homeostatic potentiation. Combining super-resolution localization microscopy and hierarchical clustering, we detect ∼10 RIMHA-Znf subclusters with ∼13 nm diameter per AZ that are compacted and increased in numbers in presynaptic homeostatic potentiation.

What are the perspectives of adults aged 18-40 living with type 2 diabetes in urban settings towards barriers and opportunities for better health and well-being: a mixed-methods study.

OBJECTIVES: Delivered as part of the global assessment of diabetes in urban settings, this study explores different aspects of living with type 2 diabetes, for adults aged 18-40. Primary questions were as follows: (1) can we identify subgroups of adults under 40 years old sharing specific perspectives towards health, well-being and living with type 2 diabetes and (2) do these perspectives reveal specific barriers to and opportunities for better type 2 diabetes prevention and management and improved well-being? DESIGN: The study employed a mixed-method design with data collected through demographic questionnaires, Q-sort statement sorting exercises, focus groups discussions and individual interviews. SETTING: Primary care across Greater Manchester, UK. PARTICIPANTS: Those aged between 18 and 40, with a confirmed type 2 diabetes diagnosis, and living in Greater Manchester were eligible to participate. A total of 46 people completed the Q-sort exercise and 43 were included in the final analysis. Of those, 29 (67%) identified as female and 32 (75%) as white. Most common time since diagnosis was between 5 and 10 years. RESULTS: The Q-sort analysis categorised 35 of the 43 participants (81%) into five subgroups. Based on average statement sorts for each subgroup, perspectives were characterised as: (1) stressed and calamity coping (n=13), (2) financially disadvantaged and poorly supported (n=12), (3) well-intentioned but not succeeding (n=5), (4) withdrawn and worried (n=2) and (5) young and stigmatised (n=3). Holistic analysis of our qualitative data also identified some common issues across these subgroups. CONCLUSIONS: Adults under 40 with type 2 diabetes are not a homogeneous group, but fall into five identifiable subgroups. They also experience issues specific to this age group that make it particularly difficult for them to focus on their own health. More tailored support could help them to make the necessary lifestyle changes and manage their type 2 diabetes better.

Blocking dPerk in the intestine suppresses neurodegeneration in a Drosophila model of Parkinson's disease.

Parkinson's disease (PD) is characterised by selective death of dopaminergic (DA) neurons in the midbrain and motor function impairment. Gastrointestinal issues often precede motor deficits in PD, indicating that the gut-brain axis is involved in the pathogenesis of this disease. The features of PD include both mitochondrial dysfunction and activation of the unfolded protein response (UPR) in the endoplasmic reticulum (ER). PINK1 is a mitochondrial kinase involved in the recycling of defective mitochondria, and PINK1 mutations cause early-onset PD. Like PD patients, pink1 mutant Drosophila show degeneration of DA neurons and intestinal dysfunction. These mutant flies also lack vital proteins due to sustained activation of the kinase R-like endoplasmic reticulum kinase (dPerk), a kinase that induces the UPR. Here, we investigated the role of dPerk in intestinal dysfunction. We showed that intestinal expression of dPerk impairs mitochondrial function, induces cell death, and decreases lifespan. We found that suppressing dPerk in the intestine of pink1-mutant flies rescues intestinal cell death and is neuroprotective. We conclude that in a fly model of PD, blocking gut-brain transmission of UPR-mediated toxicity, is neuroprotective.

A brief transdiagnostic group (the take control course) compared to individual low-intensity CBT for depression and anxiety: a randomized non-inferiority trial.

Few studies have examined brief transdiagnostic groups. The Take Control Course (TCC) was developed for patients with mild to moderate common mental health problems. We examined whether TCC is non-inferior to individual low-intensity cognitive behaviour therapy (CBT) in a single-blind individually randomised parallel non-inferiority trial. The primary outcomes were depression (PHQ9) and anxiety (GAD7) at 6-month follow-up (primary outcome point) and 12-month follow-up. The non-inferiority margin that we set, based on previous trials, corresponds to approximately 3 points on the PHQ9 and approximately 2.5 points on the GAD7. Intention-to-treat (ITT) and per-protocol (PP) analyses of 6-month data of 156 randomised patients indicated that TCC was non-inferior to individual low-intensity CBT on anxiety (ITT Coefficient = 0.24; 95% CI: -1.45 to 1.92; d = 0.04; p = .79), and depression (ITT Coefficient = 0.82; 95% CI: -1.06 to 2.69; d = 0.14; p = .39) outcomes, and functioning (ITT Coefficient = 0.69; 95% CI: -2.56 to 3.94; d = 0.08; p = .68). The findings at 12 months were inconclusive and require further testing. This randomised trial provides preliminary support that TCC is not less effective than short-term individual CBT within Improving Access to Psychological Therapies (IAPT) services.

Evaluating a tool to improve engagement and recruitment of under-served groups in trials.

BACKGROUND: Despite substantial awareness that certain groups (e.g. ethnic minorities) are under-represented and under-served in trials, limited progress has been made in addressing this. As well as a public service and ethical duty to recruit and engage under-served groups in relevant research, importantly, there are clear scientific benefits, for example, increased generalisability. The key aims of the current study were to explore the following: general barriers and facilitators to enhancing the recruitment of under-served groups into trials, the usability and value of a specific tool (INCLUDE Ethnicity Framework) to support engagement and recruitment of under-served groups, and ways of engaging diverse patient, public and community involvement and engagement (PCIE) groups. METHODS: Firstly, researchers completed a brief survey in relation to a specific trial in which they were involved (N = 182, 38% response rate). A second stage involved sampling survey respondents and asking them to complete the INCLUDE Ethnicity Framework and then a remote semi-structured interview (N = 15). Qualitative data were analysed using thematic analysis. Finally, we conducted a consultation process with PCIE contributors primarily to develop guidelines for discussing the INCLUDE Ethnicity Framework with PCIE representatives. RESULTS: Researchers recognised the importance of increasing engagement and recruitment of under-served groups within trials, but varied in their knowledge, ability and commitment to implementation in practice. The INCLUDE Ethnicity Framework was described by some as raising their awareness of how inclusion could be improved. Respondents highlighted a need for shared resources and wider structural change to facilitate such engagement. PCIE was identified, in the survey and interviews, as the most common method of trying to improve recruitment of under-served groups. However, researchers also commonly highlighted that PCIE groups were sometimes not very diverse. CONCLUSIONS: There is a need for researchers to consider the funding and time resources required for diverse and inclusive recruitment to trials and for funders to enable this. The INCLUDE Ethnicity Framework can help to raise awareness of inclusion challenges. This study indicates that it is important to take proactive steps to involve relevant under-served groups in PCIE and practical suggestions are made to facilitate this.

Self-report measures of secure attachment in adulthood: A systematic review.

BACKGROUND: Secure attachment in adulthood is associated with many markers of adaptive functioning. Valid and reliable self-report measures of attachment security could provide a practical tool to help advance strengths-based research and clinical work. Previous reviews have not specifically examined the psychometric properties of self-report instruments with respect to secure attachment or systematically appraised the methodological quality of relevant validation studies. METHOD: A systematic review was completed in accordance with the COSMIN guidelines for reviews of patient-reported outcome measures. The methodological quality of individual studies was evaluated, and results were rated against criteria for good measurement properties. RESULTS: A total of 40 studies were included in the review, which collectively reported on 24 self-report instruments. The methodological quality of individual studies was variable, and no single instrument was identified as having sufficient evidence of a range of psychometric properties. However, the Attachment Style Questionnaire-Short Form (ASQ-SF), the Cartes-Modèles Individuels de Relations (CAMIR), Cartes-Modèles Individuels de Relations-Reduced (CAMIR-R), and the Psychological Treatment Inventory-Attachment Style Scales (PTI-ASS) had the most robust evidence for the properties assessed. CONCLUSION: Existing self-report measures assessing adult secure attachment have limited psychometric support. More methodologically robust studies of content validity, reliability, measurement invariance, and construct validity in particular are needed.

The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release.

Humans carrying the CORD7 (cone-rod dystrophy 7) mutation possess increased verbal IQ and working memory. This autosomal dominant syndrome is caused by the single-amino acid R844H exchange (human numbering) located in the 310 helix of the C2A domain of RIMS1/RIM1 (Rab3-interacting molecule 1). RIM is an evolutionarily conserved multi-domain protein and essential component of presynaptic active zones, which is centrally involved in fast, Ca2+-triggered neurotransmitter release. How the CORD7 mutation affects synaptic function has remained unclear thus far. Here, we established Drosophila melanogaster as a disease model for clarifying the effects of the CORD7 mutation on RIM function and synaptic vesicle release. To this end, using protein expression and X-ray crystallography, we solved the molecular structure of the Drosophila C2A domain at 1.92 Šresolution and by comparison to its mammalian homologue ascertained that the location of the CORD7 mutation is structurally conserved in fly RIM. Further, CRISPR/Cas9-assisted genomic engineering was employed for the generation of rim alleles encoding the R915H CORD7 exchange or R915E, R916E substitutions (fly numbering) to effect local charge reversal at the 310 helix. Through electrophysiological characterization by two-electrode voltage clamp and focal recordings we determined that the CORD7 mutation exerts a semi-dominant rather than a dominant effect on synaptic transmission resulting in faster, more efficient synaptic release and increased size of the readily releasable pool but decreased sensitivity for the fast calcium chelator BAPTA. In addition, the rim CORD7 allele increased the number of presynaptic active zones but left their nanoscopic organization unperturbed as revealed by super-resolution microscopy of the presynaptic scaffold protein Bruchpilot/ELKS/CAST. We conclude that the CORD7 mutation leads to tighter release coupling, an increased readily releasable pool size and more release sites thereby promoting more efficient synaptic transmitter release. These results strongly suggest that similar mechanisms may underlie the CORD7 disease phenotype in patients and that enhanced synaptic transmission may contribute to their increased cognitive abilities.

Perspectives of people living with dementia and their care partners about the impact on social health when participating in a co-designed Dementia café.

Those diagnosed with dementia and those who provide care and support often feel socially isolated with limited opportunities for social engagement, increasing the potential for loneliness and further isolation that is detrimental to social health. This study examined how a co-designed dementia café impacted on the self-reported social health of community dwelling people with dementia and their care partners in the North-West of England. Semi-structured interviews were conducted at two time periods (summer of 2019 and spring of 2020), with five people living with dementia and eight care partners. The key finding was that participating in the cafés led to a sense of belonging and purpose that was beneficial to well-being and social health for all participants. Community-based initiatives that provide opportunities for peer support for the person with the diagnosis and the care partner are essential so that people living with dementia may rebuild their confidence as well as retaining opportunities to socialise.

A feasibility study of the impact of a communication-skills course, 'Empowered Conversations', for care partners of people living with dementia.

OBJECTIVES: To examine the feasibility, acceptability and impact of an experiential course for family care partners of people living with dementia, Empowered Conversations (EC). This study aimed to assess the impact of participation in an EC course on care partner stress levels, communication and mentalization (a form of relational-based empathy). METHOD: This study uses an uncontrolled pre-post-follow-up design. Follow-up was at 4-months after the initial EC session where baseline data were collected. One hundred and fifty-nine care partners were recruited. EC is a training course that has been designed to improve care partner communication, well-being and relationships. It is based on an integrative framework that targets the specific psychological, relationship and communication needs of carers. This framework informs targeted strategies and interactive exercises that facilitate carers to consider the goals and emotions of those they are caring for, alongside their own goals and emotions, and to use this to maximize good communication. RESULTS: Stress was significantly reduced across the three time points. Communication significantly improved across time. There were no significant changes in reflective functioning (mentalization). DISCUSSION: This study provides preliminary evidence that a communication-skills training course for care partners of people living with dementia is an acceptable and feasible intervention and has an impact both post-intervention and at follow-up. These findings require validation in a rigorous, randomized study.

A qualitative evaluation of the impact of a Good Life Club on people living with dementia and care partners.

BACKGROUND: Research suggests there is a lack of post-diagnostic support to enable people living with dementia to fulfil social and active lives throughout their dementia journey. Gardening has been found to have many benefits for people living with dementia. Although such research is important, most research frames people with dementia as passive recipients of stimulation. Research into the impact of a community-based gardening group, where people living with dementia are active in the development of an outdoor space, is underdeveloped. Knowledge about the impact of participating in such groups is also sparse. The Good Life Club (GLC) was co-developed and evaluated to respond to these gaps. OBJECTIVES: The primary aim of this article is to present the findings regarding the impact of attending the GLC on the self-reported well-being for people living with dementia and care partners. METHODS: Qualitative data were collected via 22 semi-structured interviews. Fourteen interviews were conducted before the GLC and eight after the GLC. Thematic analysis was used to analyse data. Dementia Care Mapping data were collected to supplement the interview data. FINDINGS: Four key themes were identified. The first was that participants considered having active participation in social life to be a key aspect of living a good life. The second was that the way that the GLC was set up and delivered gave the participants ownership of the GLC and within this they felt able to contribute. The third was the importance of social connectedness and peer support to the well-being of both people living with dementia and care partners. Fourth, positive mood and well-being was directly experienced through gardening. CONCLUSIONS: The combination of long-term investment of time and energy to the GLC, ongoing friendships and in-session autonomy act as key ingredients in creating a group that is relaxed, full of humour and highly valued.

Communication Empowerment Framework: An integrative framework to support effective communication and interaction between carers and people living with dementia.

OBJECTIVES: To demonstrate the power of integrating three theoretical perspectives (Mentalization Theory, Perceptual Control Theory and the Communicative Impact model), which jointly illuminate the communication challenges and opportunities faced by family carers of people with dementia. To point the way to how this framework informs the design and delivery of carer communication and interaction training. METHOD: Conceptual synthesis based on a narrative review of relevant literature, supported by examples of family carers. RESULTS: We use the conceptual models to show how the capacity to mentalize ("holding mind in mind") offers a greater sense of control over internal and external conflicts, with the result that they can be deescalated in pursuit of mutual goals. CONCLUSIONS: The integrative conceptual framework presented here highlights specific psychological and relational mechanisms that can be targeted through carer training to enhance communication with a person living with dementia.

Clients' experiences of one-to-one low-intensity interventions for common mental health problems: An interpretative phenomenological analysis.

OBJECTIVES: Common mental health disorders such as depression and anxiety are highly prevalent and carry significant health care and economic burdens. The UK's improving access to psychological therapies (IAPT) initiative was developed as a cost-effective way of reducing the pernicious effects of these disorders. IAPT interventions, such as guided self-help, have been subjected to considerable quantitative evaluation. However, there has been minimal investigation into clients' experiences of the one-to-one low-intensity interventions (LIIs), which form a key component of IAPT service provision. Qualitative exploration could provide rich data regarding experiences of psychological change and factors affecting therapeutic experiences. This will enable informative, client led insights into how low-intensity therapy can be improved. METHODS: Interpretative phenomenological analysis of eight semi-structured interviews was used to develop an idiosyncratic understanding of clients' experiences of one-to-one LIIs following entry into a randomized control trial (RCT). RESULTS: Four superordinate themes were identified from clients' accounts: goals and expectations of therapy, beneficial aspects of therapy, non-beneficial aspects of therapy, and the experience of psychological change. A heuristic model of interrelationships between factors is proposed. CONCLUSIONS: Both therapeutic techniques and relationships contribute to beneficial therapeutic experiences. The results reported here can be used to inform practice by harnessing the most beneficial aspects of therapy, such as developing adaptive therapeutic approaches to clients' clinical needs and facilitating idiosyncratic processes of psychological change. Due to limited qualitative research in this area, further research should be conducted in different service settings to assess differences and similarities in clients' experiences. PRACTITIONER POINTS: Therapists who adapted to clients' individual needs were perceived as more effective than those who did not. Effective therapeutic experiences were exemplified by a personal therapeutic approach, enough time to discuss issues and normalizing client's experiences. Clients develop idiosyncratic models of change which should be encouraged by therapists over and above clinical models.

Experiences of a transdiagnostic group, the Take Control Course, for clients with common mental health problems: A qualitative study.

OBJECTIVES: Despite the promising effectiveness findings for transdiagnostic groups, studies have not explored clients' experiences. There is a risk that clients could perceive that the content of transdiagnostic groups is not sufficiently tailored to their specific problems. Our aims were to examine whether a brief transdiagnostic group, the Take Control Course (TCC), was acceptable to participants and to explore participants' perceptions of psychological change. METHODS: Qualitative data were collected via 12 semistructured, in-depth interviews. Data collection and thematic analysis were concurrent and iterative. RESULTS: Three superordinate themes were identified: "Style and format," "Control and flexibility," and "Change." The flexible group format was appreciated, as participants felt able to engage at their own pace and adapt relevant aspects. Greater clarity regarding what was within participants' control reduced distress and enabled effective pursuit of valued goals. Participants described significant (predominantly gradual) changes, including substantial improvements within relationships. CONCLUSIONS: The transdiagnostic format did not prevent participants experiencing the TCC as individually relevant. The flexibility and consistent theoretical framework seemed to contribute to this. The results indicated that greater consideration of control and mindfulness allowed greater cognitive flexibility, an ability to reprioritize and let go of unhelpful habits, which better enabled participants to meet their goals. Implications for group therapy include (a) clearly explaining the format of such groups to clients and (b) providing flexibility in the way the group is delivered where possible. Additional qualitative studies of transdiagnostic groups are required to establish if themes generalize to other transdiagnostic groups.

Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae.

The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress-induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large-scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large-scale rearrangements. Copyright © 2017 John Wiley & Sons, Ltd.

Substrate preference of Gen endonucleases highlights the importance of branched structures as DNA damage repair intermediates.

Human GEN1 and yeast Yen1 are endonucleases with the ability to cleave Holliday junctions (HJs), which are proposed intermediates in recombination. In vivo, GEN1 and Yen1 function secondarily to Mus81, which has weak activity on intact HJs. We show that the genetic relationship is reversed in Drosophila, with Gen mutants having more severe defects than mus81 mutants. In vitro, DmGen, like HsGEN1, efficiently cleaves HJs, 5΄ flaps, splayed arms, and replication fork structures. We find that the cleavage rates for 5΄ flaps are significantly higher than those for HJs for both DmGen and HsGEN1, even in vast excess of enzyme over substrate. Kinetic studies suggest that the difference in cleavage rates results from a slow, rate-limiting conformational change prior to HJ cleavage: formation of a productive dimer on the HJ. Despite the stark difference in vivo that Drosophila uses Gen over Mus81 and humans use MUS81 over GEN1, we find the in vitro activities of DmGen and HsGEN1 to be strikingly similar. These findings suggest that simpler branched structures may be more important substrates for Gen orthologs in vivo, and highlight the utility of using the Drosophila model system to further understand these enzymes.