Adolescent Violence in the Home Among Youth Presenting to an Early Psychosis Service: An Exploration of Contributing Factors.

Adolescent violence in the home is a growing public health issue and remains under reported and under-researched. The focus of the present research is to investigate factors that may contribute to adolescent violence in the home, among acohort of young people with co-occurring early psychosis. Data relates to 50 young people (16 females, 33 males, 1 nonbinary) aged from 16-25 who were clients at a youth early psychosis service in Melbourne, Australia. Results from a discriminant function analysis revealed the two major contributing factors to whether someone used violence in the home, were whether a young person had a coexisting neurodevelopmental or intellectual disability and whether they used violence outside the home. The findings provide preliminary evidence that engaging in violence outside the home and the presence of a neurodevelopmental or intellectual disability may make it more likely for young people with early psychosis to use violence in the home.

Integrating Substance Misuse Specialists in a Youth Early Psychosis Service: Increasing Mental Health Clinicians' Knowledge and Confidence.

Substance misuse and mental health disorders are commonly occurring co-morbidities in young people. This paper reports on a pilot project to embed three specialist Alcohol and Other Drug (AoD) workers to be embedded in a youth early psychosis service to upskill mental health clinicians in managing substance misuse. Evaluation of the project used a mixed methods approach. Quantitative results showed that clinical staff members' knowledge of substance misuse, knowledge of AoD treatments and services, and overall confidence in working with young people with a substance misuse issue improved following implementation of the project. Qualitative results indicated four themes which emerged: defining the role of the AoD workers; support and upskilling of the mental health staff; openness and effective communication between the embedded workers and mental health teams; and barriers to collaboration. The results provide support for the embedding of specialist alcohol and drug workers in youth mental health services.

"What makes discovery college different?" a co-produced analysis of student experiences of discovery college.

BACKGROUND: Recovery colleges are an education-based approach to supporting mental health recovery that incorporate the voice of both lived and living experience, and experience by training in their design, production, and delivery. AIMS: To understand students' experiences of attending a youth-focused 'discovery college' course. Specifically, to see whether students were satisfied with the course, whether the learning goals of the courses were met, and what students felt makes discovery college different. METHODS: A mixed methods design analysed quantitative data on students' ratings of the course and their learning goals. A co-produced thematic analysis, incorporating the voice of lived and living experience, was also conducted on students' responses to the question "what makes discovery college different?" RESULTS: Overall, students rated their experience with the course very positively, and mostly met the learning goals of courses. The co-produced thematic analysis revealed students valued the incorporation of lived and living experience in courses, the lack of power imbalance between teachers and students, and felt it was a safe space to share and learn. CONCLUSIONS: Findings support the delivery of the recovery college model within a youth setting, and highlights this as a useful initiative in engaging people from a range of perspectives in education about mental health.

Single session family therapy for beginners: what difference does it make to psychiatry registrars to participate in family sessions in front of and behind the screen?

OBJECTIVE: Current competencies required for fellowship of the RANZCP require psychiatry registrars to have experience in working with clients across all age groups, as well as working with families and the client's wider network, however gaining this experience is not always easy for trainees. This paper reports on the experience of participating in Single Session Family Therapy (SSFT) during registrar training as a different modality for learning. METHOD: An online survey was conducted with fourteen registrars who had participated in SSFT during their child and adolescent rotation. Qualitative and simple quantitative data were collected and analysed. RESULTS: Participating in SSFT during training was initially daunting, but had a positive effect on trainees, including influencing some towards focussing their future sub-specialisation in the child and youth area. Experience came through learning by doing, and seeing change. Registrars learnt about: understanding the role of the family; teamwork; technical skills; and gained confidence. CONCLUSIONS: Opportunities for trainees to participate in SSFT enables powerful learning beyond what can be taught in the classroom. Such opportunities may enhance registrars' perceptions of family work, and may positively influence decision about future sub-specialisation.

NMR Mapping of Disordered Segments from a Viral Scaffolding Protein Enclosed in a 23 MDa Procapsid.

Scaffolding proteins (SPs) are required for the capsid shell assembly of many tailed double-stranded DNA bacteriophages, some archaeal viruses, herpesviruses, and adenoviruses. Despite their importance, only one high-resolution structure is available for SPs within procapsids. Here, we use the inherent size limit of NMR to identify mobile segments of the 303-residue phage P22 SP free in solution and when incorporated into a ∼23 MDa procapsid complex. Free SP gives NMR signals from its acidic N-terminus (residues 1-40) and basic C-terminus (residues 264-303), whereas NMR signals from the middle segment (residues 41-263) are missing because of intermediate conformational exchange on the NMR chemical shift timescale. When SP is incorporated into P22 procapsids, NMR signals from the C-terminal helix-turn-helix domain disappear because of binding to the procapsid interior. Signals from the N-terminal domain persist, indicating that this segment retains flexibility when bound to procapsids. The unstructured character of the N-terminus, coupled with its high content of negative charges, is likely important for dissociation and release of SP during the double-stranded DNA genome packaging step accompanying phage maturation.

Dynamic Optical Coherence Tomography in Dermatology.

Optical coherence tomography (OCT) represents a non-invasive imaging technology, which may be applied to the diagnosis of non-melanoma skin cancer and which has recently been shown to improve the diagnostic accuracy of basal cell carcinoma. Technical developments of OCT continue to expand the applicability of OCT for different neoplastic and inflammatory skin diseases. Of these, dynamic OCT (D-OCT) based on speckle variance OCT is of special interest as it allows the in vivo evaluation of blood vessels and their distribution within specific lesions, providing additional functional information and consequently greater density of data. In an effort to assess the potential of D-OCT for future scientific and clinical studies, we have therefore reviewed the literature and preliminary unpublished data on the visualization of the microvasculature using D-OCT. Information on D-OCT in skin cancers including melanoma, as well as in a variety of other skin diseases, is presented in an atlas. Possible diagnostic features are suggested, although these require additional validation.

Treat me right, treat me equal: using national policy and legislation to create positive changes in local health services for people with intellectual disabilities.

BACKGROUND: Creative use of legislation can produce positive change in the lives of people with intellectual disabilities. This may be 'bottom-up' or 'top-down' or at multiple levels and with multiple stakeholders. METHOD: Using a human rights-based approach (HRBA), four initiatives to improve services for people with intellectual disabilities in the UK are described. RESULTS: The first example explains the process of co-producing a DVD and board game to enable people with intellectual disabilities to understand their human rights. The second example considers the impact of organizational culture in the process of embedding a pilot evaluation of practical, human rights-based risk assessment and management tools. A third pilot project examines how the guiding principles of Mental Health Act (MHA) (2007) for England and Wales can be operationalized using an HRBA. Finally, improving equitable access to health care through a 'top-down' process of change involving the Green Light Toolkit is reported. CONCLUSION: The authors consider how to approach the process and where to focus in the system, to realize meaningful change.

NMR structure verifies the eponymous zinc finger domain of transcription factor ZNF750.

ZNF750 is a nuclear transcription factor that activates skin differentiation and has tumor suppressor roles in several cancers. Unusually, ZNF750 has only a single zinc-finger (ZNF) domain, Z*, with an amino acid sequence that differs markedly from the CCHH family consensus. Because of its sequence differences Z* is classified as degenerate, presumed to have lost the ability to bind the zinc ion required for folding. AlphaFold predicts an irregular structure for Z* with low confidence. Low confidence predictions are often inferred to be intrinsically disordered regions of proteins, which would be the case if Z* did not bind Zn2+. We use NMR and CD spectroscopy to show that a 25-51 segment of ZNF750 corresponding to the Z* domain folds into a well-defined antiparallel ßßα tertiary structure with a pM dissociation constant for Zn2+ and a thermal stability >80 °C. Of three alternative Zn2+ ligand sets, Z* uses a CCHC rather than the expected CCHH ligating motif. The switch in the last ligand maintains the folding topology and hydrophobic core of the classical ZNF motif. CCHC ZNFs are typically associated with protein-protein interactions, raising the possibility that ZNF750 interacts with DNA through other proteins rather than directly. The structure of Z* provides context for understanding the function of the domain and its cancer-associated mutations. We expect other ZNFs currently classified as degenerate could be CCHC-type structures like Z*.

Pulse-field gradient nuclear magnetic resonance of protein translational diffusion from native to non-native states.

Hydrodynamic radii (Rh -values) calculated from diffusion coefficients measured by pulse-field-gradient nuclear magnetic resonance are compared for folded and unfolded proteins. For native globular proteins, the Rh -values increase as a power of 0.35 with molecular size, close to the scaling factor of 0.33 predicted from polymer theory. Unfolded proteins were studied under four sets of conditions: in the absence of denaturants, in the presence of 6 M urea, in 95% dimethyl sulfoxide (DMSO), and in 40% hexafluoroisopropanol (HFIP). Scaling factors under all four unfolding conditions are similar (0.49-0.53) approaching the theoretical value of 0.60 for a fully unfolded random coil. Persistence lengths are also similar, except smaller in 95% DMSO, suggesting that the polypeptides are more disordered on a local scale with this solvent. Three of the proteins in our unfolded set have an asymmetric sequence-distribution of charged residues. While these proteins behave normally in water and 6 M urea, they give atypically low Rh -values in 40% HFIP and 95% DMSO suggesting they are forming electrostatic hairpins, favored by their asymmetric sequence charge distribution and the low dielectric constants of DMSO and HFIP. While diffusion-ordered NMR spectroscopy can separate small molecules, we show a number of factors combine to make protein-sized molecules much more difficult to resolve in mixtures. Finally, we look at the temperature dependence of apparent diffusion coefficients. Small molecules show a linear temperature response, while large proteins show abnormally large apparent diffusion coefficients at high temperatures due to convection, suggesting diffusion reference standards are only useful near 25°C.

Self-compassion and social anxiety: The mediating effect of emotion regulation strategies and the influence of depressed mood.

OBJECTIVES: Self-compassion constitutes a positive way of relating towards the self that enables emotional regulation and reduces emotional distress. This research first explored differences among a sample of persons with social anxiety disorder (SAD) and groups of high socially anxious (HSA) and low socially anxious (LSA) students on self-compassion, emotion regulation, and social anxiety. We then investigated emotional regulation as a mediator of the prediction of social anxiety by self-compassion and the influence of depressed mood on those relationships. DESIGN: Study 1 compared a SAD group to matched groups of HSA and LSA students. Study 2 utilized the total sample (n = 330 students and n = 33 SAD) to test mediation. Self-compassion and emotion regulation were predictors of social anxiety and depression a covariate. RESULTS: In Study 1, the SAD group did not differ from the HSA group on most aspects of self-compassion and emotional regulation but was higher on depression. Both were lower on most measures and higher on depression than the LSA group. In Study 2, higher self-compassion predicted lower social interaction anxiety, and emotional regulation strategies mediated this effect, regardless of depression. However, for social performance anxiety, controlling for depression removed mediation. Refraining from uncompassionate responses was directly connected to social anxiety, whereas compassionate responses influenced social anxiety via emotional regulation. CONCLUSIONS: Results affirm the ameliorative role of self-compassion on social anxiety and emotion regulation strategies as mechanisms of that influence. However, self-compassion's influence was affected by depression and type of social anxiety. Also, refraining from uncompassionate self-responding appears to be of prime importance in predicting social anxiety, whereas compassionate self-responding influences social anxiety via emotion regulation.

High-resolution cryo-EM structure of the Shigella virus Sf6 genome delivery tail machine.

Sf6 is a bacterial virus that infects the human pathogen Shigella flexneri. Here, we describe the cryo-electron microscopy structure of the Sf6 tail machine before DNA ejection, which we determined at a 2.7-angstrom resolution. We built de novo structures of all tail components and resolved four symmetry-mismatched interfaces. Unexpectedly, we found that the tail exists in two conformations, rotated by ~6° with respect to the capsid. The two tail conformers are identical in structure but differ solely in how the portal and head-to-tail adaptor carboxyl termini bond with the capsid at the fivefold vertex, similar to a diamond held over a five-pronged ring in two nonidentical states. Thus, in the mature Sf6 tail, the portal structure does not morph locally to accommodate the symmetry mismatch but exists in two energetic minima rotated by a discrete angle. We propose that the design principles of the Sf6 tail are conserved across P22-like Podoviridae.

The relative benefits of nonattachment to self and self-compassion for psychological distress and psychological well-being for those with and without symptoms of depression.

OBJECTIVES: Self-compassion represents a way of interacting with the self involving kindness and a balanced approach to negative self-related stimuli that has shown to contribute to reduced depression, anxiety and stress, and increased psychological well-being. Due to the potential barriers towards self-compassion for people with depressive symptoms, the objective of the present study what to investigate whether the emerging construct of 'nonattachment to self', which reflects a flexible and balanced approach to all self-related stimuli, may be more beneficial for positive psychological outcomes than self-compassion, for individuals with depressive symptoms. METHOD: A sample 388 participants (consisting of 71 men, 317 women) aged from 18 to 77 (M = 35.33, SD = 10.81) completed an online questionnaire measuring levels of self-compassion, nonattachment to self, depressive symptoms, and well-being. RESULTS: Higher levels of both nonattachment to self and self-compassion were related to reduced psychological distress and increased psychological well-being. However, for people with at least mild depressive symptoms, nonattachment to self was found to be a stronger predictor of reduced psychological distress and increased psychological well-being than self-compassion. CONCLUSION: In conclusion, the present study suggests both nonattachment to self and self-compassion are associated with better mental health in non-clinical populations. Further, for individuals experiencing at least mild symptoms of depression, self-compassion may be less beneficial than taking a more nonattached stance towards the self. The findings have implications for the way we conceptualize self-focused attention and suggest assisting individuals to let go of their fixated, self-focused attention may be especially beneficial for individuals with depressive symptoms. PRACTITIONER POINTS: The notion of letting of attachment to the separate static self lies at the core of Buddhist psychological teachings and recent research suggests it can have a positive impact on individuals psychological well-being and ill-being Given the barriers to self-compassion experienced by individuals with depressive symptoms, nonattachment to self may represent a healthy interaction with the self than is met with less resistance than self-compassion. Due to the balanced stance of nonattachment to self towards positive and negative self-related stimuli, it may be prove to be a valuable approach to treating individuals who feel conflict with taking any form of positive or kind stance towards the self.

Self-compassion and emotional regulation as predictors of social anxiety.

OBJECTIVES: Self-compassion and emotional regulation have been identified as constructive attitudes towards the self which can reduce emotional distress. This study is the first to examine the role of a self-compassionate attitude towards the self in reducing symptoms of social anxiety. The study also explored the role of emotional regulation strategies of cognitive reappraisal (CR) and expressive suppression (ES) as mechanisms that mediate the impact of self-compassion on social anxiety. DESIGN: Structural equation modelling (SEM) was conducted on cross-sectional correlational data with MPlus version 6. METHODS: A sample of 750 undergraduate students (378 men and 372 women) completed an online survey comprised of well validated self-report measures of social anxiety, emotional regulation and self-compassion. RESULTS: Structural equation modelling showed that self-compassion predicted lower social anxiety directly and indirectly through lower ES. Higher self-compassion also predicted higher CR. Contrary to expectation, CR did not predict lower social anxiety. Exploratory analyses of self-compassion divided into Compassionate Self-responding (CSR) and Refraining from Non-compassionate Responding (RUSR) identified RUSR as a predictor of lower social anxiety directly and indirectly via ES and CR. CSR had no direct effect on social anxiety but did so indirectly via CR. CONCLUSIONS: The findings provide preliminary evidence that self-compassion can play an important role in alleviating social anxiety and that emotion regulation through ES and CR are important mechanisms of that influence. PRACTITIONER POINTS: Adopting a more compassionate attitude towards the self can reduce the symptoms of social anxiety Emotional regulation through reducing emotional suppression may be a mechanism whereby higher levels of self-compassion reduce symptoms of social anxiety. Although higher levels of self-compassion predict greater use of emotional regulation through cognitive appraisal, cognitive appraisal does not predict levels of symptoms of social anxiety The capacity to refrain from non-compassionate self-responding may reduce symptoms of social anxiety directly and indirectly through lower levels of emotional suppression and greater cognitive reappraisal (CR). However, compassionate self-responding only influences symptoms of social anxiety through CR.

Cost-sharing effects on adherence and persistence for second-generation antipsychotics in commercially insured patients.

PURPOSE: To assess the relationship between patient cost-sharing (e.g., copayments or coinsurance) and adherence and persistence to second-generation (atypical) antipsychotic (SGA) medications. DESIGN AND METHODOLOGY: A retrospective, observational study of adults aged 18-64 years with schizophrenia or bipolar disorder (n = 7,910) who initiated SGA medications with employer-sponsored insurance in the 2003-2006 MarketScan Commercial Claims and Encounters Database. Adherence was defined as percent of days covered in each calendar quarter. Persistence was defined as days from initiation of SGA to the first 90-day gap in medication on-hand. Generalized Estimating Equations were used to determine the effects of cost-sharing on adherence to SGA medications based on patient-quarter data. A Cox proportional hazards model with patient cost-sharing as a time-varying covariate estimated the effects on persistence with SGA medication. PRINCIPAL FINDINGS: Higher cost-sharing was associated with a lower likelihood of adherence. When compared to plans with cost-sharing below $10, adherence rates were approximately 27% lower for patients in plans with SGA cost-sharing of $50 and above and about 10% lower for patients in plans with cost-sharing between $30 and $50. In both cases, the reduction in adherence was significant. Higher cost-sharing was also associated with a shorter time to discontinuation (HR: 1.028; 95% CI [1.006-1.051]). CONCLUSION: High SGA cost-sharing appears to be a financial barrier to SGA medication compliance, especially when cost-sharing levels exceeded $30. Our findings have implications for health plans, employers, and policymakers who have, or are, contemplating establishing cost-sharing tiers for SCA medications for commercially insured patients with serious mental illnesses.

Effects of aripiprazole on prolactin levels in subjects with schizophrenia during cross-titration with risperidone or olanzapine: analysis of a randomized, open-label study.

Hyperprolactinemia, an adverse effect associated with the use of typical antipsychotics and the atypical antipsychotic risperidone, has both acute and chronic clinical consequences. One option for clinical management is switching to an agent with a lower liability for inducing hyperprolactinemia. This post-hoc sub-analysis of an 8-week, open-label study in outpatients with schizophrenia (CN138-215) examined short-term effects on prolactin levels during a switch from risperidone or olanzapine to aripiprazole 30 mg/day. Three switch strategies were used: (I) immediate aripiprazole initiation with simultaneous immediate discontinuation of olanzapine/risperidone; (II) immediate aripiprazole initiation while tapering off olanzapine/risperidone over 14 days; (III) titrating aripiprazole upwards while tapering off olanzapine/risperidone over 14 days. Changes in prolactin levels from baseline to each last observation carried forward time point were compared with t-tests using Bonferroni correction for multiple comparisons. This sub-analysis included 269 subjects: 105 previously treated with risperidone; 164 previously treated with olanzapine. Mean baseline prolactin levels (ng/mL) were within normal range for the three olanzapine groups (Group-I, 11.7; Group-II, 13.2; Group-III, 11.2), but above normal for the risperidone groups (Group-I, 39.7; Group-II, 48.5; Group-III, 33.5). Following aripiprazole initiation, mean prolactin levels decreased significantly (p<0.001) at week-1 and were maintained to week-8 in all groups irrespective of prior treatment. Previously elevated prolactin levels in the risperidone groups were reduced to within normal range within 1 week, irrespective of switching strategy. Tolerability was good regardless of prior medication or switching strategy. Overall, rapid decreases of prolactin levels were achieved safely with all three aripiprazole switching strategies. Reversal of hyperprolactinemia during the crossover period indicates the safety and potential utility of aripiprazole addition in patients with elevated prolactin.

Comparative utility of aripiprazole and haloperidol in schizophrenia: post hoc analysis of two 52-week, randomized, controlled trials.

BACKGROUND: Since their introduction, second-generation antipsychotics (SGAs) have become the drugs of choice for the treatment of schizophrenia. However, recent findings have questioned the benefits of SGAs over first-generation antipsychotics (FGAs). OBJECTIVE: This post hoc analysis sought to compare the utility of the SGA aripiprazole with the FGA haloperidol in patients with early-phase schizophrenia (ES) or chronic schizophrenia (CS). METHOD: Data were pooled from two identical 52-week, randomized, active comparator trials (31-98-217 and 31-98-304) of aripiprazole 20-30 mg/day versus haloperidol 7-10 mg/day. Patients in the efficacy sample were classified as having ES if they were

Testing for HIV: concise guidance.

HIV is now a treatable medical condition and the majority of those living with the virus remain fit and well on treatment. Despite this a significant number of people in the UK are unaware of their HIV infection and remain at risk to their own health and of passing their virus unwittingly on to others. Late diagnosis is the most important factor associated with HIV-related morbidity and mortality in the U.K. Testing for HIV infection is often not performed due to misconceptions held by healthcare workers even when it is clinically indicated and this contributes to missed or late diagnosis. This article summarises the recommendations from the U.K. national guidelines for HIV testing 2008. The guidelines provide the information needed to enable any clinician to perform an HIV test within good clinical practice and encourage 'normalisation' of HIV testing. The full version is available at www.bhiva.org/cmsl 222621.asp.

Parents with learning disabilities: perceived incidence and needs.

Recent literature and government guidance has highlighted the rights of parents with leaming disabilities and role of services in meeting their needs. In the present study, three focus groups were conducted involving 35 members of community health visiting teams in order to identify estimated incidence and needs of parents with learning disabilities and the needs of services in supporting them. The health visiting teams identified clinically significant numbers of parents with learning disabilities and--through qualitative focus group discussion--suggested a significant need for intervention and support for these parents, greater resources and knowledge within health visiting services, and improved interagency co-ordination and communication.

The efficacy of aripiprazole in the treatment of multiple symptom domains in patients with acute schizophrenia: a pooled analysis of data from the pivotal trials.

OBJECTIVE: To examine the efficacy of aripiprazole across symptoms in patients with acute exacerbation of schizophrenia or schizoaffective disorder. METHODS: Data were pooled from five, 4-6-week acute studies. PANSS Total, Positive, Negative, and General Psychopathology Subscale improvements were analyzed, as well as all 30 individual PANSS items. RESULTS: Aripiprazole had statistically significant decreases versus placebo on PANSS subscales at Week 4, similar to those seen with haloperidol. Aripiprazole-treated patients also showed significant decreases versus placebo in 26 of the 30 PANSS items (all p<0.05). CONCLUSION: Aripiprazole demonstrates statistically and clinically significant efficacy across a range of symptoms in schizophrenia.

Somnolence effects of antipsychotic medications and the risk of unintentional injury.

PURPOSE: This study examined the relationship between antipsychotic medications, categorized by published somnolence effects, and unintentional injury (UI). METHODS: The study population included patients of 18-64 years of age in a healthcare insurance database with claims from 2001 to 2004 and diagnoses of schizophrenia or affective disorder. A nested case-control design was used with cases defined by an E-code claim (a specified external cause of injury) for selected UIs. For cases, the index date referred to the first injury. For controls, the "control index date" was the date of claim if there was only a single medical claim; for patients with > or =2 claims, one was selected at random as the "control index date." Both groups had a prescription for a first-generation antipsychotic (FGA) or second-generation antipsychotic (SGA) overlapping the index date. Potential somnolence effects were defined as: low (referent)--aripiprazole/ziprasidone; medium--risperidone; high--olanzapine/quetiapine: or any single FGA. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for UI, adjusted for gender, age, concomitant drug, and psychiatric diagnosis. RESULTS: Among 648 cases and 5214 controls, high-somnolence SGAs were associated with an OR of 1.41 95%CI (1.03-1.93) for risk of UI, while medium-somnolence SGAs, and FGAs had ORs of 1.17 95%CI (0.83-1.64) and 1.17 95%CI (0.79-1.74), respectively. When quetiapine and olanzapine were disaggregated, ORs were 1.61 95%CI (1.15-2.25) and 1.25 95%CI (0.89-1.74), respectively. CONCLUSIONS: High-somnolence SGAs may lead to UI among patients. When prescribing antipsychotics, clinicians should consider potential somnolence.