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BACKGROUND: The psychological therapies service (PTS) in the Northern Health and Social Care Trust, in Northern Ireland, provides therapies to adults with moderate or severe mental health difficulties. Psychometric outcomes data are routinely collected to assess if a patient demonstrates significant improvement in their main presenting problem area following therapy. The wider impact of therapy is not fully measured in the outcomes database as this would be disproportionately burdensome for both patient and therapist. The present study, to our knowledge, is the first to use data linkage to link patient therapy outcomes data with prescriptions data. AIMS: To widen our understanding of patient medication use before and after therapy. METHOD: Using Health and Care Number as a unique identifier, the Psychological Therapies Service - Routine Outcome Measurement Database (n = 3625) and data from 72 500 controls were linked with data from the Enhanced Prescribing Database (EPD). The EPD data were sourced from the Honest Broker Service. RESULTS: Key findings from the study were: (a) the odds of PTS clients using antipsychotics in the year before therapy were 25 times greater compared with controls (odds ratio (OR) = 24.53, 95% CI 20.16-29.84); (b) in the 1st year post discharge, PTS clients who clinically improved post therapy discharge were more likely than 'non-engagers' and 'non-improvers' to come off antianxiety medication (OR = 0.61, 95%, CI 0.38-0.98); and (c) therapy did not have an impact on antidepressant use. CONCLUSIONS: The results highlight the need for discussion between therapy services, GPs and psychiatry about whether more engagement and collaboration is needed to plan phased reduction in medication.
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Cuidados Posteriores , Alta del Paciente , Adulto , Humanos , Antidepresivos/uso terapéutico , Salud Mental , Almacenamiento y Recuperación de la InformaciónRESUMEN
Alongside the recognized potential negative repercussions of working as a psychological therapist, there is growing interest in the potential positive impacts of engaging in such work. The current study used a cross-sectional online survey design to explore the impact of a range of demographic, work-related, and compassion-related factors on levels of secondary traumatic stress (STS) and vicarious posttraumatic growth (VPTG) in an international sample of 359 psychological therapists. Hierarchical multiple regressions demonstrated that burnout, lower levels of self-compassion, having a personal trauma history, reporting a higher percentage of working time with a trauma focus, and being female were the statistically significant contributors to STS scores, explaining 40.8% of the variance, F(9, 304) = 23.2, p <.001. For VPTG, higher compassion satisfaction, higher self-compassion, higher STS, a higher percentage of working time with a trauma focus, fewer years qualified, being male, and having a personal trauma history were all statistically significant contributors, explaining 27.3% of the variance, F (10, 304) = 11.37, p <.001. The findings illustrate the potential risk and protective factors for developing STS and clarify factors that may increase the likelihood of experiencing VPTG. Implications for psychological therapists and the organizations and institutions for which they work are considered along with potential directions for future research in the discussion.
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Agotamiento Profesional , Desgaste por Empatía , Crecimiento Psicológico Postraumático , Trastornos por Estrés Postraumático , Humanos , Masculino , Femenino , Desgaste por Empatía/psicología , Estudios Transversales , Agotamiento Profesional/psicología , Empatía , Encuestas y CuestionariosRESUMEN
BACKGROUND: Cross-sectional studies have shown that the COVID-19 pandemic has had a significant impact on the mental health of healthcare staff. However, it is less well understood how working over the long term in successive COVID-19 waves affects staff well-being. AIMS: To identify subpopulations within the health and social care staff workforce with differentiated trajectories of mental health symptoms during phases of the COVID-19 pandemic. METHOD: The COVID-19 Staff Wellbeing Survey assessed health and social care staff well-being within an area of the UK at four time points, separated by 3-month intervals, spanning November 2020 to August 2021. RESULTS: Growth mixture models were performed on the depression, anxiety and post-traumatic stress disorder longitudinal data. Two class solutions provided the best fit for all models. The vast majority of the workforce were best represented by the low-symptom class trajectory, where by symptoms were consistently below the clinical cut-off for moderate-to-severe symptoms. A sizable minority (13-16%) were categorised as being in the high-symptom class, a group who had symptom levels in the moderate-to-severe range throughout the peaks and troughs of the pandemic. In the depression, anxiety and post-traumatic stress disorder models, the high-symptom class perceived communication from their organisation to be less effective than the low-symptom class. CONCLUSIONS: This research identified a group of health service staff who reported persistently high mental health symptoms during the pandemic. This group of staff may well have particular needs in terms of the provision of well-being support services.
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OBJECTIVE: Cognitive models posit negative trauma appraisals as maintaining symptoms of posttraumatic stress disorder. Recent research has demonstrated that alienation appraisals (feeling disconnected from the self and others) are salient in trauma-related distress. Studies show that alienation appraisals fully mediated the relationship between trauma exposure and symptoms of posttraumatic stress disorder (PTSD) in trauma-exposed adults. This study explored alienation appraisals in student and clinical samples, assessing whether alienation significantly mediated the relationship between cumulative trauma and trauma-related distress. It also explored whether alexithymia, social support, and loneliness also mediated the relationship between cumulative trauma and markers of trauma-related distress, clarifying the role of alienation. METHOD: Mediation and hierarchical regression models were tested with questionnaire data from a student sample (N = 100) and clinical sample of trauma-exposed treatment-seeking adults (N = 93). RESULTS: In the student sample, alienation (B = 1.27) fully mediated the relationship between cumulative trauma and posttraumatic stress, but not depression. When alexithymia, social support, and loneliness were entered as parallel mediators, only alienation appraisals (B = 1.03) significantly mediated the relationship between cumulative trauma and posttraumatic stress. For the clinical sample, alienation appraisals (ß = .53) were the only significant predictor of posttraumatic stress, while alienation appraisals (ß = .75) and, to a lesser extent, social support (ß = .19) and loneliness (ß = .30) significantly predicted depression. CONCLUSIONS: Alienation was a salient predictor of posttraumatic distress. Clinical assessment of alienation appraisals is recommended to inform psychological interventions for trauma survivors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Trastornos por Estrés Postraumático , Adulto , Emociones , Humanos , Apoyo Social , Trastornos por Estrés Postraumático/psicología , Encuestas y Cuestionarios , SobrevivientesRESUMEN
Background: Healthcare staff represent a high-risk group for mental health difficulties as a result of their role during the COVID-19 pandemic. A number of wellbeing initiatives have been implemented to support this population, but remain largely untested in terms of their impact on both the recipients and providers of supports.Objective: To examine the experience of staff support providers in delivering psychological initiatives to healthcare staff, as well as obtain feedback on their perceptions of the effectiveness of different forms of support.Method: A mixed methods design employing a quantitative survey and qualitative focus group methodologies. An opportunity sample of 84 psychological therapists providing psychological supports to Northern Ireland healthcare staff participated in an online survey. Fourteen providers took part in two focus groups.Results: The majority of providers rated a number of supports as useful (e.g. staff wellbeing helplines, Hospital In-reach) and found the role motivating and satisfying. Thematic analysis yielded five themes related to provision of support: (1) Learning as we go, applying and altering the response; (2) The 'call to arms', identity and trauma in the collective response; (3) Finding the value; (4) The experience of the new role; and (5) Moving forward.Conclusions: While delivering supports was generally a positive experience for providers, adaptation to the demands of this role was dependent upon important factors (e.g. clinical experience) that need to be considered in the planning phase. Robust guidance should be developed that incorporates such findings to ensure effective evidence-based psychological supports are available for healthcare staff during and after the pandemic.
Providers of wellbeing supports to healthcare staff during COVID-19 viewed them as useful and the role satisfying.Key factors (e.g. clinical experience) should be considered to make the role manageable.Guidance should be developed to ensure appropriate supports are delivered.
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OBJECTIVES: With the acceptance of Complex Post-Traumatic Stress Disorder (Complex PTSD) as a recognized diagnosis, supporters of unimodal approaches to traditional PTSD (e.g., trauma-focused cognitive behavioral therapies) claim that these modalities should be extended to Complex PTSD, whereas other practitioners stress the need for more gradual phase-oriented treatment plans within this population. This article examines the extant literature base and arguments for each position. METHOD: A critical literature review and commentary on the clinical area. FINDINGS: Both therapy perspectives appear to share more commonalities than differences in routine clinical practice. Several issues raised by each therapeutic approach (e.g., lack of evidence base, destabilizing effects on complex clients) may be artifacts of clinician identity and examples of a "straw man" fallacy rather than legitimate concerns. CONCLUSIONS: An alternative synthesized view may be more helpful in advancing the area of Complex PTSD rather than a perpetuation of long-held polarized opinions. Adopting this stance, the present article makes a number of research recommendations to increase understanding of both unimodal and phased interventions. Suggestions for clinical practice, including a focus on bespoke formulations, and enhanced training programs for Complex PTSD to assist this consolidation process are also discussed. Clinical Impact Statement: Two conflicting perspectives on Complex PTSD therapy include: 1) "unimodal" therapies such as Cognitive behavioral Therapy are effective in traditional PTSD; and 2) "phase-oriented" therapies that have less supporting evidence, but take a more gradual pace due to the challenging nature of Complex PTSD, are more appropriate in such clinical presentations. The present commentary provides clarity for clinicians on the evidence base and clinical viewpoints relevant to both positions, revealing that these 2 perspectives have more in common than previously considered. The article will help clinicians consider more blended practices when treating Complex PTSD, and provides recommendations for research and practice to develop this area. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Terapia Cognitivo-Conductual , Trastornos por Estrés Postraumático , Humanos , Masculino , Trastornos por Estrés Postraumático/terapiaRESUMEN
BACKGROUND: Throughout the coronavirus disease 2019 (COVID-19) pandemic, health and social care workers have faced unprecedented professional demands, all of which are likely to have placed considerable strain on their psychological well-being. AIMS: To measure the national prevalence of mental health symptoms within healthcare staff, and identify individual and organisational predictors of well-being. METHOD: The COVID-19 Staff Wellbeing Survey is a longitudinal online survey of psychological well-being among health and social care staff in Northern Ireland. The survey included four time points separated by 3-month intervals; time 1 (November 2020; n = 3834) and time 2 (February 2021; n = 2898) results are presented here. At time 2, 84% of respondents had received at least one dose of a COVID-19 vaccine. The survey included four validated psychological well-being questionnaires (depression, anxiety, post-traumatic stress and insomnia), as well as demographic and organisational measures. RESULTS: At time 1 and 2, a high proportion of staff reported moderate-to-severe symptoms of depression (30-36%), anxiety (26-27%), post-traumatic stress (30-32%) and insomnia (27-28%); overall, significance tests and effect size data suggested psychological well-being was generally stable between November 2020 and February 2021 for health and social care staff. Multiple linear regression models indicated that perceptions of less effective communication within their organisation predicted greater levels of anxiety, depression, post-traumatic stress and insomnia. CONCLUSIONS: This study highlights the need to offer psychological support to all health and social care staff, and to communicate with staff regularly, frequently and clearly regarding COVID-19 to help protect staff psychological well-being.
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Public speaking anxiety (PSA) is a prevalent condition which is highly interrelated with social anxiety. PSA can be effectively treated with exposure therapy. Virtual reality exposure therapy (VRET) is increasingly being explored as a novel and cost-effective mode of treatment. No previous randomized controlled trial has examined whether stand-alone 360° video VRET is an effective intervention for treating PSA and interrelated disorder relevant fears. Further, studies have not explored whether 360° video content influences VRET outcomes. Participants with high PSA (n = 51) were randomly allocated to: 360° video VRET incorporating stimuli of audiences (360°Audience) (n = 17), 360° video VRET incorporating stimuli of empty rooms (360°Empty) (n = 16) and no treatment control (n = 18). Outcomes were measured over five time-points. Mixed ANOVA revealed a significant interaction between time and intervention group for PSA, social anxiety and fear of negative evaluation (FNE). Within-group analysis demonstrated there was a significant pre-intervention to post-intervention reduction across measures for both 360° video VRET groups: PSA 360°Audience (ηp2 = .90, p<.001), 360°Empty (ηp2 = .71, p < .001); social anxiety 360°Audience (ηp2 = .49, p=.002), 360°Empty (ηp2 = .39, p = .009); FNE 360°Audience (ηp2 = .59, p<.001), 360°Empty (ηp2 = .43, p = .006). Active intervention participants showed significant improvement from pre-intervention to 10-week follow-up on all measures. Findings illustrate that 360° video VRET is an efficacious way to significantly reduce PSA, social anxiety and FNE.
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Trastornos Fóbicos , Terapia de Exposición Mediante Realidad Virtual , Ansiedad/terapia , Trastornos de Ansiedad , Humanos , Trastornos Fóbicos/terapia , HablaRESUMEN
BACKGROUND: Whilst data-driven processing (DDP) during trauma has been shown to play a role in poor memory integration and is associated with post-traumatic stress disorder (PTSD) re-experiencing symptoms, the pre-trauma risk factors and related cognitive mechanisms are uncertain. AIMS: This experimental study aimed to investigate predictors of peri-traumatic DDP, as well as its role in attention bias to threat and free recall. METHOD: A virtual reality video was used to simulate an analogue trauma. Questionnaires, a free recall task, and an eye-tracking measure assessed cognitive changes after exposure. RESULTS: Regression analysis demonstrated that trait dissociation at pre-exposure to trauma significantly predicted DDP. Attention bias towards threat-related images was found. Results showed that DDP and poorer free recall predicted attention bias to threat images and higher levels of DDP actually predicted higher overall scores in the free recall task. CONCLUSIONS: This study showed that DDP is strongly linked to dissociative traits, and along with memory disintegration it may predict attention changes after exposure to a trauma.
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Sesgo Atencional , Trastornos por Estrés Postraumático , Atención , Trastornos Disociativos , Humanos , Recuerdo MentalRESUMEN
Rates of posttraumatic stress are elevated in individuals who have experienced childhood and/or cumulative trauma, and trauma appraisals have been suggested as a possible mediator of this effect. This study tested the proposed mediating role of trauma appraisals between both childhood and cumulative trauma, and two markers of trauma-related distress; posttraumatic stress and depression. Mediation models were developed and tested with data collected from a sample of trauma-exposed, treatment receiving adults (N = 106). Trauma appraisals fully mediated relationships between childhood trauma and PTSD/depression. Appraisals also mediated the relationships between cumulative trauma and depression. When appraisal subscales were simultaneously entered, alienation appraisals were the only significant mediator of these relationships. The study found support for the proposed mediating role of trauma appraisals between different forms of trauma and trauma related distress. Alienation appraisals were particularly emphasised.
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BACKGROUND: The Salkovskis (1999) model of obsessive compulsive disorder (OCD), which emphasizes the role of inflated responsibility, has proven highly influential in both the understanding and treatment of OCD. AIMS: This study aimed to empirically test several core processes of this model. METHOD: The individual components of the model were measured using multiple indicators in a sample of undergraduate students (n = 170), and confirmatory factor analyses were used to ascertain the most reliable, valid and theoretically consistent latent variables. Structural equation modelling was used to test proposed relations between latent constructs in the model. RESULTS: The inflated responsibility model was a good fit for the data in the present sample. As predicted by the model, misinterpretations of intrusive thoughts as indicating personal responsibility fully mediated the relationships between responsibility beliefs and counterproductive safety strategies, neutralizing actions and mood changes. CONCLUSIONS: The Salkovksis (1999) inflated responsibility model of OCD is empirically supported in the present sample of undergraduate students, lending support to the proposed mechanisms in the model and supporting prior evidence.
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Trastorno Obsesivo Compulsivo , Cognición , Análisis Factorial , Humanos , Reproducibilidad de los Resultados , Conducta SocialRESUMEN
OBJECTIVE: Exposure to traumatic events is prevalent, with the impact of trauma and its relationship with other conditions widely documented. Research suggests that clinicians do not routinely ask about trauma history in clinical settings. Trauma-related training has been recommended as a means of addressing this. Neither the impact of training on clinician behavior (i.e., frequency of asking about or detection of trauma history) nor the relationship between training and these variables have been formally reviewed. METHOD: A systematic literature review was conducted using PsycINFO, Scopus, and Web of Science. The grey literature and reference lists of included articles were consulted. Nine articles met the eligibility criteria for inclusion. RESULTS: Two-thirds of studies reported statistically significant evidence to suggest that trauma-related training is related to (1) increased frequency of asking about trauma history and (2) greater detection of trauma history. CONCLUSIONS: While acknowledging the limited number and variable quality of studies, as well as the failure to detect statistical significance in all studies, this review provides some evidence that trauma-related training is related to clinician inquiry and detection of trauma history. Further high-quality research is needed. Training should address barriers to inquiry, acknowledge the potential variation in inquiry behavior across trauma subtypes, and encompass a skill and educational approach to both inquiry and response to trauma. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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Exposición a la Violencia , Personal de Salud , Servicios de Salud Mental , Trauma Psicológico/diagnóstico , Personal de Salud/educación , Personal de Salud/estadística & datos numéricos , Humanos , Servicios de Salud Mental/normas , Servicios de Salud Mental/estadística & datos numéricosRESUMEN
Exertional limb pain is a common problem encountered in recreational and competitive athletes. Affecting both the upper and lower extremities, this broad entity can be musculoskeletal, vascular, neurologic, oncologic, or infectious in origin. This article focuses on the vascular causes of exercise-related extremity pain, which encompass a cadre of elusive diagnoses. Specifically, we examine arterial endofibrosis, popliteal artery entrapment syndrome, and chronic exertional compartment syndrome of both the upper and lower extremities. For each of these conditions, we offer updates regarding the respective epidemiology, common signs and symptoms, worthwhile diagnostic modalities, and pertinent treatment options, all based on evidence and reports published over the past year.
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Arteriopatías Oclusivas/complicaciones , Traumatismos en Atletas/diagnóstico , Síndromes Compartimentales/complicaciones , Dolor/diagnóstico , Dolor/etiología , Arterias/patología , Atletas , Fibrosis , Humanos , Extremidad Inferior/fisiopatología , Extremidad Superior/fisiopatologíaRESUMEN
This study used interpretative phenomenological analysis (IPA) to explore the lived experiences of five individuals diagnosed with obsessive-compulsive disorder (OCD) who underwent a group cognitive behavioral therapy (CBT) intervention program to address their symptoms. Two master themes were identified: experiences and processes of change and reflections on change. For all participants, the degree of group cohesion or connectedness they established with group members emerged as highly important in facilitating therapeutic progress. A number of technical elements of cognitive behavioral therapy (CBT) were also notable therapeutic factors, including questioning/rationalizing maladaptive interpretations about intrusions. However, the commonality of non-specific group processes as key features for subsequent therapeutic change prompts the need for further research in dynamics within CBT group interventions for OCD.
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Dyslexia has been associated with a range of psychological well-being issues in childhood. However, it is unclear if these difficulties stem from coping with academic struggles at school, or from other pre-existing diagnoses that sometimes co-occur with dyslexia. Using UK Millennium Cohort Study data (n = 7224) from 2003 to 2011, the present study compared psychological well-being development from ages 3-11 years for children with (1) dyslexia only; (2) special educational needs excluding dyslexia; (3) comorbid dyslexia and other special educational needs; and (4) no special educational needs. Growth curve modelling results controlling for race, gender, age and family income suggested that with the exception of conduct difficulties, psychological well-being issues related to dyslexia do not occur preschool; rather, they commence upon starting school. Copyright © 2017 John Wiley & Sons, Ltd.
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Adaptación Psicológica , Personas con Discapacidad/psicología , Dislexia/psicología , Niño , Preescolar , Estudios de Cohortes , Educación Especial , Femenino , Humanos , Discapacidades para el Aprendizaje/psicología , Masculino , Instituciones AcadémicasRESUMEN
OBJECTIVES: Elevated shame and dissociation are common in dissociative identity disorder (DID) and chronic posttraumatic stress disorder (PTSD) and are part of the constellation of symptoms defined as complex PTSD. Previous work examined the relationship between shame, dissociation, and complex PTSD and whether they are associated with intimate relationship anxiety, relationship depression, and fear of relationships. This study investigated these variables in traumatized clinical samples and a nonclinical community group. METHOD: Participants were drawn from the DID (n = 20), conflict-related chronic PTSD (n = 65), and nonclinical (n = 125) populations and completed questionnaires assessing the variables of interest. A model examining the direct impact of shame and dissociation on relationship functioning, and their indirect effect via complex PTSD symptoms, was tested through path analysis. RESULTS: The DID sample reported significantly higher dissociation, shame, complex PTSD symptom severity, relationship anxiety, relationship depression, and fear of relationships than the other two samples. Support was found for the proposed model, with shame directly affecting relationship anxiety and fear of relationships, and pathological dissociation directly affecting relationship anxiety and relationship depression. The indirect effect of shame and dissociation via complex PTSD symptom severity was evident on all relationship variables. CONCLUSION: Shame and pathological dissociation are important for not only the effect they have on the development of other complex PTSD symptoms, but also their direct and indirect effects on distress associated with relationships.
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Ansiedad/psicología , Depresión/psicología , Trastornos Disociativos/psicología , Miedo/psicología , Relaciones Interpersonales , Parejas Sexuales/psicología , Vergüenza , Trastornos por Estrés Postraumático/psicología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Cognitive models of posttraumatic stress disorder (PTSD) place an emphasis on the role of negative appraisals of traumatic events. It is suggested that the way in which the event is appraised determines the extent to which posttraumatic stress symptoms will be experienced. Therefore, a strong relationship between trauma appraisals and symptoms of PTSD might be expected. However, this relationship is not as firmly established in the child and adolescent literature. A systematic literature review of this relationship returned 467 publications, of which 11 met full eligibility criteria. A random effects meta-analysis revealed a large effect size for the relationship between appraisals and PTSD symptoms in children and adolescents, r = .63, 95% CI [.58, .68], Z = 17.32, p < .001, with significant heterogeneity present. A sensitivity analysis suggested that this relationship was not contingent on 1 specific measure of appraisals. Results were consistent with the cognitive behavioral theory of PTSD, demonstrating that appraisals of trauma are strongly related to posttraumatic stress in children and adolescents. However, this relationship was not observed in a sample of 4- to 6-year-olds, indicating that further research is required to explicate cognitive processing of trauma in very young children.
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Trauma Psicológico/psicología , Adolescente , Niño , Preescolar , Humanos , Modelos Psicológicos , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/psicologíaRESUMEN
OBJECTIVES: To conduct a preliminary study comparing different trauma and clinical populations on types of shame coping style and levels of state shame and guilt. METHODS: A mixed independent groups/correlational design was employed. Participants were recruited by convenience sampling of 3 clinical populations-complex trauma (n = 65), dissociative identity disorder (DID; n = 20), and general mental health (n = 41)-and a control group of healthy volunteers (n = 125). All participants were given (a) the Compass of Shame Scale, which measures the four common shame coping behaviors/styles of "withdrawal," "attack self," "attack other," and "avoidance," and (b) the State Shame and Guilt Scale, which assesses state shame, guilt, and pride. RESULTS: The DID group exhibited significantly higher levels of "attack self," "withdrawal," and "avoidance" relative to the other groups. The complex trauma and general mental health groups did not differ on any shame variable. All three clinical groups had significantly greater levels of the "withdrawal" coping style and significantly impaired shame/guilt/pride relative to the healthy volunteers. "Attack self" emerged as a significant predictor of increased state shame in the complex trauma, general mental health, and healthy volunteer groups, whereas "withdrawal" was the sole predictor of state shame in the DID group. CONCLUSIONS: DID emerged as having a different profile of shame processes compared to the other clinical groups, whereas the complex trauma and general mental health groups had comparable shame levels and variable relationships. These differential profiles of shame coping and state shame are discussed with reference to assessment and treatment. (PsycINFO Database Record
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Adaptación Psicológica , Trastornos Mentales , Vergüenza , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Exposición a la Guerra/efectos adversos , Adulto JovenRESUMEN
Central challenges in the design of large and dynamic macromolecular assemblies for synthetic biology lie in developing effective methods for testing design strategies and their outcomes, including comprehensive assessments of solution behavior. We created and validated an advanced design of a 600-kDa protein homododecamer that self-assembles into a symmetric tetrahedral cage. The monomeric unit is composed of a trimerizing apex-forming domain genetically linked to an edge-forming dimerizing domain. Enhancing the crystallographic results, high-throughput small-angle x-ray scattering (SAXS) comprehensively contrasted our modifications under diverse solution conditions. To generate a phase diagram associating structure and assembly, we developed force plots that measure dissimilarity among multiple SAXS data sets. These new tools, which provided effective feedback on experimental constructs relative to design, have general applicability in analyzing the solution behavior of heterogeneous nanosystems and have been made available as a web-based application. Specifically, our results probed the influence of solution conditions and symmetry on stability and structural adaptability, identifying the dimeric interface as the weak point in the assembly. Force plots comparing SAXS data sets further reveal more complex and controllable behavior in solution than captured by our crystal structures. These methods for objectively and comprehensively comparing SAXS profiles for systems critically affected by solvent conditions and structural heterogeneity provide an enabling technology for advancing the design and bioengineering of nanoscale biological materials.
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Processive, ring-shaped protein and nucleic acid protein translocases control essential biochemical processes throughout biology and are considered high-prospect therapeutic targets. The Escherichia coli Rho factor is an exemplar hexameric RNA translocase that terminates transcription in bacteria. As with many ring-shaped motor proteins, Rho activity is modulated by a variety of poorly understood mechanisms, including small-molecule therapeutics, protein-protein interactions, and the sequence of its translocation substrate. Here, we establish the mechanism of action of two Rho effectors, the antibiotic bicyclomycin and nucleic acids that bind to Rho's primary RNA recruitment site. Using small-angle X-ray scattering and a fluorescence-based assay to monitor the ability of Rho to switch between open-ring (RNA-loading) and closed-ring (RNA-translocation) states, we found bicyclomycin to be a direct antagonist of ring closure. Reciprocally, the binding of nucleic acids to its N-terminal RNA recruitment domains is shown to promote the formation of a closed-ring Rho state, with increasing primary-site occupancy providing additive stimulatory effects. This study establishes bicyclomycin as a conformational inhibitor of Rho ring dynamics, highlighting the utility of developing assays that read out protein conformation as a prospective screening tool for ring-ATPase inhibitors. Our findings further show that the RNA sequence specificity used for guiding Rho-dependent termination derives in part from an intrinsic ability of the motor to couple the recognition of pyrimidine patterns in nascent transcripts to RNA loading and activity.