Role of the HCF-1 Basic Region in Sustaining Cell Proliferation

BACKGROUND: The human herpes simplex virus-associated host cell factor 1 (HCF-1) is a conserved human transcriptional co-regulator that links positive and negative histone modifying activities with sequence-specific DNA-binding transcription factors. It is synthesized as a 2035 amino acid precursor that is cleaved to generate an amino- (HCF-1(N)) terminal subunit, which promotes G1-to-S phase progression, and a carboxy- (HCF-1(C)) terminal subunit, which controls multiple aspects of cell division during M phase. The HCF-1(N) subunit contains a Kelch domain that tethers HCF-1 to sequence-specific DNA-binding transcription factors, and a poorly characterized so called "Basic" region (owing to a high ratio of basic vs. acidic amino acids) that is required for cell proliferation and has been shown to associate with the Sin3 histone deacetylase (HDAC) component. Here we studied the role of the Basic region in cell proliferation and G1-to-S phase transition assays. METHODOLOGY/PRINCIPAL FINDINGS: Surprisingly, much like the transcriptional activation domains of sequence-specific DNA-binding transcription factors, there is no unique sequence within the Basic region required for promoting cell proliferation or G1-to-S phase transition. Indeed, the ability to promote these activities is size dependent such that the shorter the Basic region segment the less activity observed. We find, however, that the Basic region requirements for promoting cell proliferation in a temperature-sensitive tsBN67 cell assay are more stringent than for G1-to-S phase progression in an HCF-1 siRNA-depletion HeLa-cell assay. Thus, either half of the Basic region alone can support G1-to-S phase progression but not cell proliferation effectively in these assays. Nevertheless, the Basic region displays considerable structural plasticity because each half is able to promote cell proliferation when duplicated in tandem. Consistent with a potential role in promoting cell-cycle progression, the Sin3a HDAC component can associate independently with either half of the Basic region fused to the HCF-1 Kelch domain. CONCLUSIONS/SIGNIFICANCE: While conserved, the HCF-1 Basic region displays striking structural flexibility for controlling cell proliferation

Are 3D printed models acceptable in assessment?

BACKGROUND: Three-dimensional (3D) printed models are increasingly used in undergraduate anatomy teaching. However, their role and value in anatomy assessment remains under consideration. The aim of this study was to evaluate student and educator perspectives on acceptability of using novel 3D printed heart models for assessment. METHODS: We used printed 3D models of the heart for first-year medical students, in small group teaching, formative assessment and revision at home. We adopted a mixed methods approach involving questionnaires, then focus groups to collect student and educator views. We used QSR Nvivo to manage thematic analysis of responses, carried out by student and educators, respectively. FINDINGS: Overall, students 89% (n = 75/84) and educators 91% (n = 10/11) found the assessment acceptable. Thematic analysis of focus groups (n = 4 students, n = 5 educators) identified five key perceptions shared across student and educator groups: 3D models are the future, realism is valued, models appear feasible, consistent and provide a potential for a range of applications in assessment. DISCUSSION: There was agreement between educators and students that the use of 3D heart models was acceptable. Key recognised benefits include accessibility and consistency across settings, made more relevant in the current COVID-19 pandemic. We recommend integration of 3D models into teaching and assessment for educational alignment and careful selection of anatomy to model. Further research is required to explore the use of models in summative assessments

Adapting an intervention of brief problem-solving therapy to improve the health of women with antenatal depressive symptoms in primary healthcare in rural Ethiopia

Background: Evidence-based brief psychological interventions are safe and effective for the treatment of antenatal depressive symptoms. However, the adaptation of such interventions for low- and middle-income countries has not been prioritised. This study aimed to select and adapt a brief psychological intervention for women with antenatal depressive symptoms attending primary healthcare (PHC) in rural Ethiopia. Methods: We employed the Medical Research Council (MRC) framework for the development and evaluation of complex interventions. Alongside this, we used the ADAPT-ITT model of process adaptation and the ecological validity model (EVM) to guide content adaptation. We conducted formative work, comprising a qualitative study, a series of three participatory theories of change workshops and an expert adaptation workshop to assess the needs of the target population and to select an intervention for adaptation. The adaptation process followed a series of steps: (1) training Ethiopian mental health experts in the original South African problem-solving therapy (PST version 0.0) and an initial adaptation workshop leading to PST Version 1.0. (2) Version 1.0 was presented to perinatal women and healthcare professionals in the form of a ‘theatre test’, leading to further adaptations (version 2.0). (3) Local and international stakeholders reviewed version 2.0, leading to version 3.0, which was used to train 12 PHC staff using clinical cases. (4) Finally, feedback about PST version 3.0 and its delivery was obtained from PHC staff. Results: In the first step, we modified case examples and terminology from the South African model, introduced an in-session pictorial flipchart for this low literacy setting, and added strategies to facilitate women’s engagement before translating into Amharic. In the second step, adaptations included renaming of the types of problems and inclusion of more exercises to demonstrate proposed coping strategies. In the third step, the components of motivational interviewing were dropped due to cultural incongruence. In the final step, refresher training was delivered as well as additional training on supporting control of women’s emotions to address PHC staff training needs, leading to the final version (version 4.0). Conclusion: Using a series of steps, we have adapted the content and delivery of brief PST to fit the cultural context of this setting. The next step will be to assess the feasibility and acceptability of the intervention and its delivery in antenatal care settings

The effect of anger rumination on cardiovascular responses during self-anger and other-anger

The high morbidity and mortality associated with cardiovascular (CV) disease have led to a profusion of research into its etiology. With only 50% of the variance in risk associated with traditional risk factors, research has begun to focus more on psychological and behavioral risk factors to improve treatment and prevention options for CV disease. CV reactivity and recovery following an emotional stressor such as anger has been proposed as possible explanations for the relationship between negative emotional stressors and CV health through prolonged activation of the autonomic stress response. One proposed factor that may contribute to prolonged autonomic activation following anger includes anger rumination, which is the tendency to have unintentional and recurrent thoughts about anger experiences after the anger experience has ended. While previous research has shown that engaging in anger rumination following anger is associated with longer recovery time and continued experiences of anger (e.g., Gerin et al., 2006), no research has focused on CV responses following anger in which no one was to blame, such as being angry with one’s self. The present studied examined the role of state and trait anger rumination and state and trait negative affect on CV recovery time after having 75 healthy undergraduate students (ages 18-44) write about two anger experiences in a repeated-measures design: one in which they had been angry with someone else (other-anger) and another in which they had been angry with themselves (self-anger). Path analysis results revealed that trait anger rumination, but not state anger rumination, was a significant direct predictor of longer CV recovery time following the other-anger writing task, but the same pattern was not observed following the self-anger writing task. Furthermore, trait negative affect was significantly but negatively associated with CV recovery time for both self-anger and other-anger, indicating that higher trait negative affect was associated with faster CV recovery time. The findings from the present study suggest that although both writing tasks were associated with significant changes in CV responses and self-reported state negative affect, the influence of trait anger rumination on CV responses may only operate when the anger was caused by someone else. While the proposed model was not supported in the present study, findings do suggest self-anger is common and is associated with similar CV responses to those seen in other-anger. Thus, further research is warranted to examine potential psychological factors that may underlie self-anger and its concomitant CV responses

COVID-19 experience of people with severe mental health conditions and families in South Africa

BACKGROUND: People with severe mental health conditions, such as schizophrenia, and their family caregivers are underserved in low- and middle-income countries where structured psychosocial support in the community is often lacking. This can present challenges to recovery and for coping with additional strains, such as a pandemic.AIM: This study explored the experiences and coping strategies of people with lived experience of a severe mental health condition, and family caregivers, in South Africa during the initial stages of the coronavirus disease 2019 (COVID-19) pandemic.SETTING: This qualitative study was conducted in the Nelson Mandela Bay District, Eastern Cape, South Africa, in the most restrictive period of the COVID-19 lockdown.METHODS: Telephonic qualitative interviews were conducted with people with lived experience ( n = 14) and caregivers ( n = 15). Audio recordings were transcribed and translated to English from isiXhosa. Thematic analysis was conducted with NVivo 12. RESULTS: Participants described negative impacts including increased material hardship, intensified social isolation and heightened anxiety, particularly among caregivers who had multiple caregiving responsibilities. Coping strategies included finding ways to not only get support from others but also give support, engaging in productive activities and taking care of physical health. The main limitation was inclusion only of people with access to a telephone.CONCLUSION: Support needs for people with severe mental health conditions and their families should include opportunities for social interaction and sharing coping strategies as well as bolstering financial security.CONTRIBUTION: These findings indicate that current support for this vulnerable group is inadequate, and resource allocation for implementation of additional community-based, recovery-focused services for families must be prioritised.</p

Psychological type and attitude towards Celtic Christianity among committed Churchgoers in the United Kingdom: an empirical study

This article takes the burgeoning interest in Celtic Christianity as a key example of the way in which churches may be responding to the changing spiritual and religious landscape in the United Kingdom today and examines the power of psychological type theory to account for variation in the attitude of committed churchgoers to this innovation. Data provided by a sample of 248 Anglican clergy and lay church officers (who completed the Francis Psychological Type Scales together with the Attitude toward Celtic Christianity Scale) demonstrated that intuitive types, feeling types, and perceiving types reported a more positive attitude towards Celtic Christianity than sensing types, thinking types, and judging types. These findings are interpreted to analyse the appeal of Celtic Christianity and to suggest why some committed churchgoers may find this innovation less attractive

Peer-led recovery groups for people with psychosis in South Africa (PRIZE):protocol for a randomised controlled feasibility trial

Background: The available care for people with psychosis in South Africa is inadequate to support personal recovery. Group peer support interventions are a promising approach to foster recovery, but little is known about the preferences of service users, or the practical application of this care model, in low- and middle-income countries (LMIC). This study aims to assess the acceptability and feasibility of integrating peer-led recovery groups for people with psychosis and their caregivers in South Africa into existing systems of care, and to determine key parameters in preparation for a definitive trial. Methods: The study is set in Nelson Mandela Bay Metropolitan district of the Eastern Cape Province, South Africa. The design is an individually randomised parallel group feasibility trial comparing recovery groups in addition to treatment as usual (TAU) with TAU alone in a 1:1 allocation ratio. We aim to recruit 100 isiXhosa-speaking people with psychosis and 100 linked caregivers. TAU comprises anti-psychotic medication-focused outpatient care. The intervention arm will comprise seven recovery groups, including service users and caregiver participants. Recovery groups will be delivered in two phases: a 2-month phase facilitated by an auxiliary social worker, then a 3-month peer-led phase. We will use mixed methods to evaluate the process and outcomes of the study. Intervention acceptability and feasibility (primary outcomes) will be assessed at 5 months post-intervention start using qualitative data collected from service users, caregivers, and auxiliary social workers, along with quantitative process indicators. Facilitator competence will be assessed with the GroupACT observational rating tool. Trial procedures will be assessed, including recruitment and retention rates, contamination, and validity of quantitative outcome measures. To explore potential effectiveness, quantitative outcome data (functioning, unmet needs, personal recovery, internalised stigma, health service use, medication adherence, and caregiver burden) will be collected at baseline, 2 months, and 5 months post-intervention start. Discussion: This study will contribute to the sparse evidence on the acceptability and feasibility of peer-led and recovery-oriented interventions for people with psychosis in LMIC when integrated into existing care systems. Results from this feasibility trial will inform preparations for a definitive trial and subsequent larger-scale implementation. Trial registration: Pan-African Clinical Trials Register PACTR202202482587686. Registered on 28 February 2022. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=21496

Brief problem-solving therapy for antenatal depressive symptoms in primary care in rural Ethiopia:protocol for a randomised, controlled feasibility trial

BACKGROUND: Despite a high prevalence of antenatal depression in low- and middle-income countries, there is very little evidence for contextually adapted psychological interventions delivered in rural African settings. The aims of this study are (1) to examine the feasibility of procedures for a future fully powered efficacy trial of contextually adapted brief problem solving therapy (PST) for antenatal depression in rural Ethiopia, and (2) to investigate the acceptability, fidelity and feasibility of delivery of PST in routine antenatal care.METHODS: Design: A randomised, controlled, feasibility trial and mixed method process evaluation.PARTICIPANTS: Consecutive women attending antenatal clinics in two primary care facilities in rural Ethiopian districts. Eligibility criteria: (1) disabling levels of depressive symptoms (Patient Health Questionnaire (PHQ-9) score of five or more and positive for the 10th disability item); (2) gestational age 12-34 weeks; (3) aged 16 years and above; (4) planning to live in the study area for at least 6 months; (5) no severe medical or psychiatric conditions.INTERVENTION: Four sessions of adapted PST delivered by trained and supervised antenatal care staff over a maximum period of eight weeks.CONTROL: enhanced usual care (EUC).SAMPLE SIZE: n = 50. Randomisation: individual randomisation stratified by intimate partner violence (IPV). Allocation: central phone allocation. Outcome assessors and statistician masked to allocation status. Primary feasibility trial outcome: dropout rate. Primary future efficacy trial outcome: change in PHQ-9 score, assessed 9 weeks after recruitment.SECONDARY OUTCOMES: anxiety symptoms, trauma symptoms, intimate partner violence, disability, healthcare costs at 9 weeks; postnatal outcomes (perinatal and neonatal complications, onset of breast feeding, child health) assessed 4-6 weeks postnatal. Other trial feasibility indicators: recruitment, number and duration of sessions attended. Audio-recording of randomly selected sessions and in-depth interviews with purposively selected participants, healthcare providers and supervisors will be analysed thematically to explore the acceptability and feasibility of the trial procedures and fidelity of the delivery of PST.DISCUSSION: The findings of the study will be used to inform the design of a fully powered efficacy trial of brief PST for antenatal depression in routine care in rural Ethiopia.TRIAL REGISTRATION: The protocol was registered in the Pan-African clinical trials registry, (PACTR): registration number: PACTR202008712234907 on 18/08/2020; URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9578

Predatory Publishing: What You Don’t Know CAN Hurt You

Predatory publishers recruit faculty and graduate students to publish in their seemingly high quality journals that frequently lack peer review, charge fees, and have poor reputations. Tenure-track nursing faculty with publishing expectations may be especially vulnerable to the inviting emails received from predatory publishers. Nurse educators should collaborate with their health sciences librarians to identify and implement strategies to combat predatory publishers in nursing education and research