An improved auxin-inducible degron system preserves native protein levels and enables rapid and specific protein depletion.

Rapid perturbation of protein function permits the ability to define primary molecular responses while avoiding downstream cumulative effects of protein dysregulation. The auxin-inducible degron (AID) system was developed as a tool to achieve rapid and inducible protein degradation in nonplant systems. However, tagging proteins at their endogenous loci results in chronic auxin-independent degradation by the proteasome. To correct this deficiency, we expressed the auxin response transcription factor (ARF) in an improved inducible degron system. ARF is absent from previously engineered AID systems but is a critical component of native auxin signaling. In plants, ARF directly interacts with AID in the absence of auxin, and we found that expression of the ARF PB1 (Phox and Bem1) domain suppresses constitutive degradation of AID-tagged proteins. Moreover, the rate of auxin-induced AID degradation is substantially faster in the ARF-AID system. To test the ARF-AID system in a quantitative and sensitive manner, we measured genome-wide changes in nascent transcription after rapidly depleting the ZNF143 transcription factor. Transcriptional profiling indicates that ZNF143 activates transcription in cis and regulates promoter-proximal paused RNA polymerase density. Rapidly inducible degradation systems that preserve the target protein's native expression levels and patterns will revolutionize the study of biological systems by enabling specific and temporally defined protein dysregulation.

Novel hyperpigmentation pathophysiology following a prolonged course of imipramine therapy.

Imipramine is a tricyclic antidepressant typically reserved for patients with treatment-resistant mood disorders. A rare side effect of long-term use of imipramine is a slowly progressive melanin-associated, slate gray-blue hyperpigmentation of the skin in a photo-distributed pattern. We report a case of imipramine-induced hyperpigmentation developing 50 years after initiating imipramine therapy, whose lesions were essentially devoid of melanin on histopathological exam. This differs from all other reported cases of imipramine-induced hyperpigmentation in two notable respects. First, the time between initiating imipramine therapy and the onset of pigmentation changes was nearly 30 years longer than prior case reports. Second, the lack of melanin in our samples suggests a divergence from the hypothesized melanin-imipramine complex mechanism of hyperpigmentation. Instead, we propose a novel pathogenesis of imipramine-induced hyperpigmentation that is unrelated to melanin.

Erythema elevatum diutinum in a patient with well-controlled Crohn disease.

Erythema elevatum diutinum is a rare, chronic cutaneous leukocytoclastic vasculitis, with prominent fibrosis at its later stage. In this article, we report a case of erythema elevatum diutinum in a 23-year-old woman with well-controlled Crohn disease. To our knowledge, erythema elevatum diutinum has been reported in only three other cases of Crohn disease, in which eruptions of erythema elevatum diutinum were associated with features of active Crohn. Our patient was in clinical remission at the time of erythema elevatum diutinum onset, making this report significant not only for its uncommon presentation, but more importantly, to aid readers. diagnosis and clinical management of similar cases.

Examining the need for a high level of therapeutic security at a regional forensic mental health service in Aotearoa New Zealand.

The ceiling of therapeutic security in Aotearoa New Zealand is medium security. The aim of this study is to identify and characterise a putative cohort of high-secure patients at a medium-secure regional forensic mental health service. A retrospective review of all admissions to a specific service was conducted over 3.75 years. The Dangerousness Understanding, Recovery and Urgency Manual, Triage Security Scale (DUNDRUM-1) was used to identify patients with high-secure care needs. A multiple logistic regression analysis was used to identify the local needs of this cohort. We found a significant incidence (an admission every 55 days) and prevalence (11%) of mixed-gendered and culturally diverse patients with high-secure care needs. The cohort had a high prevalence of psychosis and violent offences, and relatively short length of stay. There is also an indication that the cohort was subject to more restrictive practice. A solution is proposed to meet the needs of this cohort.

Don't Go Breaking My Heart: Not Your Ordinary Tattoo Reaction.

ABSTRACT: Necrobiosis lipoidica (NL) is a rare, chronic idiopathic granulomatous dermatitis with a somewhat controversial association with diabetes and other systemic diseases. We report a case of NL developing within a polychromic tattoo on the lower leg of a 53-year-old woman. Characteristic histopathologic findings of both active and chronic "burnt-out" NL appeared to originate from the tattoo where red ink was used 13 years prior. To the best of our knowledge, only 3 other cases of tattoo-associated NL have been reported.

Standard set of patient-reported outcomes for personality disorder.

PURPOSE: The purpose of the article is to present standard set of outcomes for people with personality disorder (PD), in order to facilitate patient outcome measurement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) gathered a multidisciplinary international working group, consisting of 16 experts, including clinicians, nurses, psychologists, methodologists and patient representatives, to develop a standard set of outcome measures for people with PD. The Delphi method was used to reach consensus on the scope of the set, outcome domains, outcome measures, case-mix variables and time points for measuring outcomes in service users. For each phase, a project team prepared materials based on systematic literature reviews and consultations with experts. RESULTS: The working group decided to include PD, as defined by International Classification of Diseases 11th revision (ICD-11). Eleven core outcomes and three optional outcomes across four health domains (mental health, behaviour, functioning and recovery) were defined as those relevant for people with PD. Validated measures for the selected outcomes were selected, some covering more than one outcome. Case-mix variables were aligned to other ICHOM mental health standard sets and consisted of demographic factors and those related to the treatment that people received. The group recommended that most outcomes are measured at baseline and annually. CONCLUSION: The international minimum standard set of outcomes has the potential to improve clinical decision making through systematic measurement and comparability. This will be key in improving the standard of health care for people with PD across the world.

The Model for Understanding Inpatient Aggression: A Version for Mental Health Nurses Working in Prisons.

Preventing and managing aggression remains an important and challenging task for mental health nurses. Despite the concern, there is a dearth of frameworks to assist practice and inform assessment and intervention related to aggression, for forensic mental health nurses working in prisons. This paper presents a model for understanding aggression within prison mental health units. The model elucidates various personal and situational determinants of aggression. It offers a systematic framework for mental health nurses to investigate and understand aggression, to ultimately assist nurses to provide care in an informed and effective manner, and for services to consider structural factors that contribute to the risk of aggression.

Benchmarking to reduce restrictive practices in forensic mental health services: a Delphi study.

OBJECTIVES: Forensic mental health services (FMHS) have higher rates, duration and frequency of restrictive practices (seclusion, physical restraint and mechanical restraint). Data generated by services can be used to set targets (benchmarks) with like services to reduce or eliminate restrictive practices. The aim of this study was to develop restrictive practice benchmarks for Australian and New Zealand FMHS. METHOD: A participatory action research methodology was used by conducting a Delphi study. FMHS experts provided de-identified service-specific restrictive practice data, which was used to stimulate reflection towards the development of restrictive practice benchmarks. RESULTS: Consensus decision-making was reached on benchmarks for the rate, duration and frequency of seclusion and physical restraint. Mechanical restraint was found to be a rare event, requiring event specific review in each service. CONCLUSIONS: Benchmarking with FMHS may assist in working to reduce restrictive practices and encourage the scrutiny of service practice. Establishment of a FMHS network might assist to embed the proposed benchmarks.

Prison mental health in-reach teams in Aotearoa New Zealand: A national survey.

The STAIR in-reach model of care for prisoners with serious mental illness focuses on screening, triage, assessment, interventions and reintegration by using the principles of assertive community treatment. An evidence base exists for the efficacy for its use in Aotearoa New Zealand. However, little is known about its adoption throughout the country. This national survey of managers of in-reach teams to all prisons (N = 19) aimed to determine the pattern of in-reach service delivery. It compared STAIR in-reach teams with other teams regarding service structure, staffing, interventions, reintegration strategies and training needs. This study signals gains made by adopting the STAIR model (multi-disciplinary team service delivery, 'through the wire' support and use of technologies to assist discharge planning) and potential areas of improvement (further use of psychosocial interventions and training needs). To assist national adoption of STAIR, a review is required to consider the cultural responsivity, gender-responsivity and recovery-orientated characteristics of the model.

The appropriateness of DUNDRUM-3 and DUNDRUM-4 for Maori in forensic mental health services in New Zealand: participatory action research.

BACKGROUND: The Auckland Regional Forensic Psychiatry Services (ARFPS) in New Zealand has introduced structured clinical judgment instruments developed in Ireland (DUNDRUM-3 and DUNDRUM-4) to assist staff decision-making regarding service users' clinical pathways. In New Zealand, Maori (the indigenous people) constitute 43% of the in-patient forensic mental health population. The aim of this study was to determine the face validity of the measures for Maori. METHODS: Participatory Action Research was aligned with a kaupapa Maori (Maori-orientated) research approach, to give full recognition to Maori cultural values. Two hui (gatherings) were held with Maori clinical and cultural experts at the service. The first hui (n = 12), explored the cultural appropriateness of the measures. The second (n = 10) involved a reflection on appropriate adaptions to the measures. Discussions were digitally recorded, transcribed and thematically analysed. RESULTS: Although the usefulness of the measures in enhancing the overall quality of clinical decision-making was confirmed, the DUNDRUM measures were considered to be limited in their ability to fully measure Maori service user progress and recovery. Suggestions were made to develop an additional 'pillar' focused on cultural identity and spirituality for DUNDRUM-3; to use both service user and family ratings for the adapted DUNDRUM-3 and DUNDRUM-4 measures; and to involve cultural expertise at the point of structured clinical judgement when using the measures. CONCLUSIONS: This is the first study to consider the face validity of the DUNDRUM-3 and DUNDRUM-4 for indigenous peoples, who are internationally over-represented in forensic mental health services. Suggested changes would require a negotiated, collaborative process between Maori cultural expertise and the original authors of the measures.

NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC). While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed. Work presented here indicates that mesenchymal NSCLC upregulates glutamine-fructose-6-phosphate transaminase 2 (GFPT2). GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT). METHODS: Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC. Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion. RESULTS: Our work demonstrates that GFPT2 is transcriptionally upregulated by NF-κB and repressed by the NAD+-dependent deacetylase SIRT6. Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT. CONCLUSIONS: Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC. Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.

Comparative outcomes for a national cohort of persons convicted of murder, with and without serious mental illness, and those found not guilty by reason of insanity on a murder charge: A 25-year follow-up study.

BACKGROUND: Serious mental illness (SMI) is common among persons sentenced to life imprisonment for murder, yet little is known about how this affects rehabilitation, prospects of parole, or risk to the community. AIM: The aim of this study is to compare outcomes for a national cohort of offenders charged with murder who were either convicted and sentenced to life in prison or placed on a forensic hospital order. METHODS: The 386 cases of murder charges in New Zealand between 1988 and 2000 were divided into three groups: perpetrators without SMI sentenced to life imprisonment (n = 313), perpetrators with SMI but sentenced to life imprisonment (n = 32), or those with such illness and found not guilty by reason of insanity (NGRI) who received a forensic hospital order (n = 41). Access to rehabilitative interventions, time to release, reoffending, and recall to prison or hospital were examined. RESULTS: Being in prison but having severe mental illness delayed release on parole but did not increase the risk of criminal recidivism or recall to prison. Hospital order patients were a demographically different group; they were released to the community earlier and had a lower rate of criminal recidivism. CONCLUSIONS: This study provides some evidence that incarceration periods for life-sentenced homicide perpetrators with SMI may be reduced without increasing community risk if hospital transfer and/or more targeted interventions are provided in prison. It also provides further evidence that persons found NGRI after a charge of murder have a relatively low risk of criminal recidivism. The stigma that may sometimes attach to such offenders is unwarranted, if it relies on concerns about risk of reoffending.

The Use of Restrictive Practices on Males Released from Prison and Entering Acute Mental Health Services: A Retrospective Cross-sectional Comparative Study.

Little is understood about restrictive practices (seclusion, physical restraint, mechanical restraint) for those admitted to mental health services from prison. This study aimed to determine restrictive practices use on males admitted involuntarily from prison compared to those admitted from the community. A retrospective cross-sectional, comparative research design was used. Those admitted from prison were no more likely to experience restrictive practices; but were more likely to have a co-existing diagnosis of alcohol/substance use or personality disorder, in addition to a primary diagnosis of psychotic illness. The proportionate use of restrictive practices despite such complex presentations is potentially indicative of the clinical use of effective alternative management strategies.

Risk assessment and subsequent nursing interventions in a forensic mental health inpatient setting: Associations and impact on aggressive behaviour.

AIM AND OBJECTIVES: To examine associations between risk of aggression and nursing interventions designed to prevent aggression. BACKGROUND: There is scarce empirical research exploring the nature and effectiveness of interventions designed to prevent inpatient aggression. Some strategies may be effective when patients are escalating, whereas others may be effective when aggression is imminent. Research examining level of risk for aggression and selection and effectiveness of interventions and impact on aggression is necessary. DESIGN: Archival case file. METHODS: Data from clinical files of 30 male and 30 female patients across three forensic acute units for the first 60 days of hospitalisation were collected. Risk for imminent aggression as measured by the Dynamic Appraisal of Situational Aggression, documented nursing interventions following each assessment, and acts of aggression within the 24-hours following assessment were collected. Generalised estimating equations were used to investigate whether intervention strategies were associated with reduction in aggression. RESULTS: When a Dynamic Appraisal of Situational Aggression assessment was completed, nurses intervened more frequently compared to days when no Dynamic Appraisal of Situational Aggression assessment was completed. Higher Dynamic Appraisal of Situational Aggression assessments were associated with a greater number of interventions. The percentage of interventions selected for males differed from females; males received more pro re nata medication and observation, and females received more limit setting, one-to-one nursing and reassurance. Pro re nata medication was the most commonly documented intervention (35.9%) in this study. Pro re nata medication, limit setting and reassurance were associated with an increased likelihood of aggression in some risk bands. CONCLUSIONS: Structured risk assessment prompts intervention, and higher risk ratings result in more interventions. Patient gender influences the type of interventions. Some interventions are associated with increased aggression, although this depends upon gender and risk level. RELEVANCE TO CLINICAL PRACTICE: When structured risk assessments are used, there is greater likelihood of intervention. Intervention should occur early using least restrictive interventions.

Impact of an assertive community treatment model of care on the treatment of prisoners with a serious mental illness.

OBJECTIVES: This study aims to describe the impact of a mental health assertive community treatment prison model of care (PMOC) on improving the ability to identify prisoner needs, provide interventions and monitor their efficacy. METHODS: We carried out a file review across five prisons of referrals in the year before the implementation of the PMOC in 2010 ( n = 423) compared with referrals in the year after ( n = 477). RESULTS: Some improvements in the identification of needs and providing interventions were detected. There was increased use of medication management and clinically significant improvement in addressing engagement with families. Monthly multi-disciplinary team face-to-face contact improved. CONCLUSIONS: Meeting the needs of mentally ill prisoners is challenged by the complexity of the custodial environment. Improvements made resulted from changing the model of care, rather than adding new resources.

Adding an accredited exercise physiologist role to a new model of care at a secure extended care mental health service: a qualitative study.

BACKGROUND: Accredited exercise physiologists (AEPs) are emerging as essential members of allied health in the management of non-communicable chronic diseases. People diagnosed with severe mental illness (SMI) are at greater risk of cardiovascular diseases. Secure extended care units (SECUs) provide treatment, supervision and support for people with SMI whose needs cannot be met adequately in the community. However, the role of AEPs in SECUs has not been described. AIM: Describe the processes and outcomes of adding an AEP to a new model of care at a SECU. METHODS: An exploratory study with emphasis on qualitative data. Interviews with a purposive sample of SECU staff. RESULTS: Participants articulated concern about poor physical health of which two themes emerged (1) the development of the AEP role; a calculated gamble and (2) the practical application of the role. CONCLUSIONS: An AEP was identified as the role to best implement the organisations vision to improve physical health of people with SMI. Implementation and practical application of the role relied on an informed calculated gamble. Yet, once embedded in the service, the AEP role was able to capacity build among clinical staff, develop a treatment pathway, and implement consumer specific physical health interventions.

Post-fall reporting in aged acute inpatient mental health units: an 18-month observational cohort study.

BACKGROUND: Despite the high risk of falling for people with severe mental illness, there is limited falls research in mental health settings. Therefore, the objective of this observational cohort study was to conduct a focused post-fall review of fall episodes within aged acute inpatient mental health units at one of Australia's largest publicly funded mental health organizations. METHODS: A post-fall reporting tool was developed to collect intrinsic and extrinsic fall risk factors among three aged acute mental health inpatient units over an 18-month period. Descriptive and inferential analyses were conducted to describe fall risk factors and predictors of fall risk. RESULTS: There were a total of 115 falls, of which the tool was used for 93 (80.9%) episodes. Falls occurred most often in consumer's bedroom/bathroom and were unwitnessed. Intrinsic risk factors were most often attributed to postural drop and losing balance during walking. However, that was in contrast to consumer's who self-reported feeling dizzy as the reason of the fall. CONCLUSIONS: Based on the cohort, future falls could be reduced by targeting those aged above 82 years, or with a diagnosis of dementia. Recurrent falls during admission could be reduced by targeting those with psychotic illness and males with a diagnosis of dementia. A clearer dialogue among consumers and clinical staff reporting about fall episodes may support future remedial interventions and inform programs to reduce fall risk and assist the challenge of describing unwitnessed falls in aged acute inpatient mental health settings.

From positive screen to engagement in treatment: a preliminary study of the impact of a new model of care for prisoners with serious mental illness.

BACKGROUND: The high prevalence of serious mental illness (SMI) in prisons remains a challenge for mental health services. Many prisoners with SMI do not receive care. Screening tools have been developed but better detection has not translated to higher rates of treatment. In New Zealand a Prison Model of Care (PMOC) was developed by forensic mental health and correctional services to address this challenge. The PMOC broadened triggers for referrals to mental health teams. Referrals were triaged by mental health nurses leading to multidisciplinary team assessment within specified timeframes. This pathway for screening, referral and assessment was introduced within existing resources. METHOD: The PMOC was implemented across four prisons. An AB research design was used to explore the extent to which mentally ill prisoners were referred to and accepted by prison in-reach mental health teams and to determine the proportion of prison population receiving specialist mental health care. RESULTS: The number of prisoners in the study in the year before the PMOC (n = 9,349) was similar to the year after (n = 19,421). 24.6 % of prisoners were screened as per the PMOC in the post period. Referrals increased from 491 to 734 in the post period (Z = -7.23, p < 0.0001). A greater number of triage assessments occurred after the introduction of the PMOC (pre = 458; post = 613, Z = 4.74, p < 0.0001) leading to a significant increase in the numbers accepted onto in-reach caseloads (pre = 338; post = 426, Z = 3.16, p < 0.01). Numbers of triage assessments completed within specified time frames showed no statistically significant difference before or after implementation. The proportion of prison population on in-reach caseloads increased from 5.6 % in the pre period to 7.0 % in the year post implementation while diagnostic patterns did not change, indicating more prisoners with SMI were identified and engaged in treatment. CONCLUSIONS: The PMOC led to increased prisoner numbers across screening, referral, treatment and engagement. Gains were achieved without extra resources by consistent processes and improved clarity of professional roles and tasks. The PMOC described a more effective pathway to specialist care for people with SMI entering prison.

Australian nurses' perceptions of the use of manual restraint in the Emergency Department: a qualitative perspective.

AIMS AND OBJECTIVES: To explore emergency nurses perceptions of the use of manual restraint. BACKGROUND: Manual restraint of patients has historically been an accepted practice, though little is known about the use of manual restraint in general hospitals. DESIGN: A qualitative, descriptive, exploratory, study was undertaken. METHOD: Fifteen semi-structured interviews with emergency nurses were completed. Data were analysed using qualitative thematic analysis procedures. RESULTS: The following themes were identified: 'part of the job', 'reasons for manual restraint', 'restraint techniques', 'consequences' and 'lack of documentation'. Manual restraint occurred frequently each shift and most were not documented. This may be due to nurse's perceptions that manually restraining a patient did not comprise formal restraint and was the only option. Nurses used manual restraint to manage patients who were violent and aggressive or to perform procedures. However, they reported a lack of education and training in manual restraint. Nurses identified several consequences for the patient, staff and the organisation as a result of these events including psychological and physical injuries. CONCLUSIONS: Empirical research of prevalence and issues surrounding manual restraint events is required to inform health care organisations and government to develop, implement and evaluate appropriate policies and strategies to ensure safety of patients and staff. The employment of peer support workers and professionals with expertise in mental health and dementia may aid in the reduction of manual restraint events and improve care of all patients within the Emergency Department. Research on manual restraint in health settings is also needed. RELEVANCE TO CLINICAL PRACTICE: Nurses need to be aware that manual restraint is not just an accepted part of their work, but is a strategy of last resort that should be documented. Organisations must implement standardised educational programmes for nurses together with policies and processes to monitor and evaluate manual restraint events.

Educating emergency department nurses about trauma informed care for people presenting with mental health crisis: a pilot study.

BACKGROUND: Practicing with trauma informed care (TIC) can strengthen nurses' knowledge about the association of past trauma and the impact of trauma on the patient's current mental illness. An aim of TIC is to avoid potentially re-traumatising a patient during their episode of care. A TIC education package can provide nurses with content that describes the interplay of neurological, biological, psychological, and social effects of trauma that may reduce the likelihood of re-traumatisation. Although mental health nurses can be TIC leads in multidisciplinary environments, the translation of TIC into clinical practice by nurses working in emergency departments (EDs) is unknown. However, before ED nurses can begin to practice TIC, they must first be provided with meaningful and specific education about TIC. Therefore, the aims of this study were to; (1) evaluate the effectiveness of TIC education for ED nursing staff and (2) describe subsequent clinical practice that was trauma informed. METHODS: This project was conducted as exploratory research with a mixed methods design. Quantitative data were collected with an 18-item pre-education and post-education questionnaire. Qualitative data were collected with two one-off focus groups conducted at least three-months after the TIC education. Two EDs were involved in the study. RESULTS: A total of 34 ED nurses participated in the TIC education and 14 ED nurses participated in the focus groups. There was meaningful change (p < 0.01, r ≥ 0.35) in 9 of the 18-items after TIC education. Two themes, each with two sub-themes, were evident in the data. The themes were based on the perceived effectiveness of TIC education and the subsequent changes in clinical practice in the period after TIC education. CONCLUSION: Emergency department nurses became more informed of the interplay of trauma on an individual's mental health. However, providing care with a TIC framework in an ED setting was a considerable challenge primarily due to time constraints relative to the day-to-day ED environment and rapid turnover of patients with potentially multiple and complex presentations. Despite this, nurses understood the effect of TIC to reduce the likelihood of re-traumatisation and expressed a desire to use a TIC framework.