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Mono-O-glycosylation of target proteins by bacterial toxins or effector proteins is a well-known mechanism by which bacteria interfere with essential functions of host cells. The respective glycosyltransferases are important virulence factors such as the Clostridioides difficile toxins A and B. Here, we describe two glycosyltransferases of Yersinia species that have a high sequence identity: YeGT from the zoonotic pathogen Yersinia enterocolitica and YkGT from the murine pathogen Yersinia kristensenii. We show that both modify Rho family proteins by attachment of GlcNAc at tyrosine residues (Tyr-34 in RhoA). Notably, the enzymes differed in their target protein specificity. While YeGT modified RhoA, B, and C, YkGT possessed a broader substrate spectrum and glycosylated not only Rho but also Rac and Cdc42 subfamily proteins. Mutagenesis studies indicated that residue 177 is important for this broader target spectrum. We determined the crystal structure of YeGT shortened by 16 residues N terminally (sYeGT) in the ligand-free state and bound to UDP, the product of substrate hydrolysis. The structure assigns sYeGT to the GT-A family. It shares high structural similarity to glycosyltransferase domains from toxins. We also demonstrated that the 16 most N-terminal residues of YeGT and YkGT are important for the mediated translocation into the host cell using the pore-forming protective antigen of anthrax toxin. Mediated introduction into HeLa cells or ectopic expression of YeGT and YkGT caused morphological changes and redistribution of the actin cytoskeleton. The data suggest that YeGT and YkGT are likely bacterial effectors belonging to the family of tyrosine glycosylating bacterial glycosyltransferases.
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Proteínas de Bactérias , Tirosina , Yersinia , Glicosilação , Humanos , Yersinia/metabolismo , Yersinia/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Tirosina/metabolismo , Tirosina/química , Glicosiltransferases/metabolismo , Glicosiltransferases/genética , Glicosiltransferases/química , Proteína rhoA de Ligação ao GTP/metabolismo , Yersinia enterocolitica/metabolismo , Yersinia enterocolitica/genética , Animais , Células HeLa , Camundongos , Cristalografia por Raios X , Yersiniose/metabolismo , Yersiniose/microbiologiaRESUMO
Anxiety disorders (AD) are associated with altered connectivity in large-scale intrinsic brain networks. It remains uncertain how much these signatures overlap across different phenotypes due to a lack of well-powered cross-disorder comparisons. We used resting-state functional magnetic resonance imaging (rsfMRI) to investigate differences in functional connectivity (FC) in a cross-disorder sample of AD patients and healthy controls (HC). Before treatment, 439 patients from two German multicenter clinical trials at eight different sites fulfilling a primary diagnosis of panic disorder and/or agoraphobia (PD/AG, N = 154), social anxiety disorder (SAD, N = 95), or specific phobia (SP, N = 190) and 105 HC underwent an 8 min rsfMRI assessment. We performed categorical and dimensional regions of interest (ROI)-to-ROI analyses focusing on connectivity between regions of the defensive system and prefrontal regulation areas. AD patients showed increased connectivity between the insula and the thalamus compared to controls. This was mainly driven by PD/AG patients who showed increased (insula/hippocampus/amygdala-thalamus) and decreased (dorsomedial prefrontal cortex/periaqueductal gray-anterior cingulate cortex) positive connectivity between subcortical and cortical areas. In contrast, SAD patients showed decreased negative connectivity exclusively in cortical areas (insula-orbitofrontal cortex), whereas no differences were found in SP patients. State anxiety associated with the scanner environment did not explain the FC between these regions. Only PD/AG patients showed pronounced connectivity changes along a widespread subcortical-cortical network, including the midbrain. Dimensional analyses yielded no significant results. The results highlighting categorical differences between ADs at a systems neuroscience level are discussed within the context of personalized neuroscience-informed treatments. PROTECT-AD's registration at NIMH Protocol Registration System: 01EE1402A and German Register of Clinical Studies: DRKS00008743. SpiderVR's registration at ClinicalTrials.gov: NCT03208400.
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Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.
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Transtornos de Ansiedade , Terapia Cognitivo-Comportamental , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Adulto , Terapia Cognitivo-Comportamental/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Adulto Jovem , Terapia Implosiva/métodosRESUMO
BACKGROUND: Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub-optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment. METHODS: Data were collected from 10 clinical sites with assessments at pre-and post-treatment and at least once more at 3, 6 or 12-month follow-up. Participants were assigned to one of three groups based on diagnostic status for youths who: (a) retained an anxiety diagnosis from post to end point (minimal responders); (b) remitted anxiety diagnoses at post but relapsed by end point (relapsed responders); and (c) retained a diagnosis at post but remitted to be diagnosis free at end point (delayed responders). Growth curve models assessed patterns of change over time for the three groups and examined predictors associated with these patterns including demographic, clinical and parental factors, as well as treatment factors. RESULTS: Higher primary disorder severity, being older, having a greater number of anxiety disorders, having social anxiety disorder, as well as higher maternal psychopathology differentiated the minimal responders from the delayed and relapsed responders at the baseline. Results from the growth curve models showed that severity of the primary disorder and treatment modality differentiated patterns of linear change only. Higher severity was associated with significantly less improvement over time for the minimal and relapsed response groups, as was receiving group CBT, when compared to the delayed response group. CONCLUSIONS: Sub-optimal response patterns can be partially differentiated using variables assessed at pre-treatment. Increased understanding of different patterns of change following treatment may provide direction for clinical decision-making and for tailoring treatments to specific groups of clinically anxious youth. Future research may benefit from assessing progress during treatment to detect emerging response patterns earlier.
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INTRODUCTION: This study examined the long-term effectiveness of cognitive behavioral therapy (CBT) (≥ 2 years after the end of therapy) in the routine care of youth (mean 11.95 years; SD = 3.04 years) with primary anxiety disorder (AD). METHODS: Two hundred and ten children with any AD as a primary diagnosis and with any comorbidity were included in the "Kids Beating Anxiety (KibA)" clinical trial and received evidence-based CBT. Diagnoses, severity of diagnoses, and further dimensional outcome variables of symptoms and functioning were assessed before (baseline), after the last treatment session (POST), and at two follow-up (FU) assessments in the child and caregiver report: 6 months (6MONTHS-FU) and >2 years (mean 4.31; SD = 1.07 years) after the last treatment session (long-term FU). RESULTS: At POST, 61.38% showed total remission of all and any ADs. At long-term FU, the remission rate was 63.64%. Compared to baseline, ratings of severity, anxiety, impairment/burden, and life quality improved significantly after CBT in child and caregiver report. All pre-post/FU improvements and global success ratings were stable in child (Pre-Post: Hedges' g = 3.57; Pre-6MONTHS-FU: Hedges' g = 3.43; Pre-LT-FU: Hedges' g = 2.34) and caregiver report (Pre-Post: Hedges' g = 2.00; Pre-6MONTHS-FU: Hedges' g = 2.31; Pre-LT-FU: Hedges' g = 2.31) across all POST- and FU-assessment points. Some outcomes showed further significant improvement, and no deterioration was found over the course of time. Effect sizes calculated in the present study correspond to, or even exceed, effect sizes reported in previous meta-analysis. CONCLUSIONS: Stable long-term effects of "KibA" CBT for youth with ADs, comparable to those results from efficacy studies, were achieved in a routine practice setting by applying treatment manuals tested in randomized controlled trials. These findings are remarkable, as the patient group studied here consisted of an age group within the main risk phase of developing further mental disorders, and therefore an increase in new-onset anxiety and further mental disorders would be expected over the long time span studied here.
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Assistência Ambulatorial , Transtornos de Ansiedade , Terapia Cognitivo-Comportamental , Humanos , Terapia Cognitivo-Comportamental/métodos , Transtornos de Ansiedade/terapia , Feminino , Masculino , Criança , Adolescente , Assistência Ambulatorial/métodos , Resultado do Tratamento , Qualidade de VidaRESUMO
Imagining anticipated affects can foster future-oriented behavior in adults. However, children often still have difficulties in vividly imagining how they will feel in a specific episode (affective episodic future thinking [EFT]). We investigated whether enacting anticipated affects helps children to imagine how they will feel and whether this enhances proactive behavior in turn. A total of 90 5-year-old children were randomly assigned to one of three groups. In the embodiment group, children were instructed to imagine and physically enact how positive and negative they would feel in an upcoming performance test. Children in the EFT-only group underwent a similar procedure but did not enact their future affect. In the control group, children were reminded of the upcoming test only without receiving a prompt to imagine the upcoming test. After the manipulation, children had the opportunity to play one of three games. One game was relevant for the test. Children's choice to play the relevant game in advance of the test served as an indicator for proactive behavior. Mechanisms (e.g., detailedness of the envisioned event) and moderators (theory of mind and neuroticism) of the link between embodied EFT and proactive behavior were explored. Children in the embodiment group chose the relevant game above chance level, but they did not choose the relevant game more often than children in the EFT-only group and the control group. Those results were independent of the assumed mediators and moderators.
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INTRODUCTION: Adherence to COVID-19 mitigation measures is an important vehicle that has contributed to the fight against the pandemic. The present study investigated potential changes of the level of adherence and its predictors between 2020 and 2021 in eight countries. METHODS: Adherence to COVID-19 measures and its potential predictors (perception of usefulness of the measures, rating of the governmental COVID-19 communication, mental health variables, COVID-19 burden) were compared between representative population samples from European Union countries (France, Germany, Poland, Spain, Sweden) and non-European Union countries (Russia, UK, USA) assessed in 2020 (N = 7,658) and 2021 (N = 8,244). RESULTS: In the overall sample, multiple analyses of variance revealed significantly higher levels of adherence to the measures, their perception as useful, positive mental health, and feelings of being well supported and well informed by governments in 2020 than in 2021. In contrast, feelings of being left alone and symptoms of depression, anxiety, and stress were significantly higher in 2021 than in 2020. In France, Poland, Spain, and the UK, the adherence level was significantly higher in 2020 than in 2021. In European Union countries, ratings of governmental communication were less positive, and levels of mental health were lower in 2021 than in 2020. In non-European countries, an opposite result pattern was found. CONCLUSION: The current results indicate a decrease in adherence to the mitigation measures and factors that could foster it. Potential ways how governments and authorities could enhance the population's trust in COVID-19 mitigation measures are discussed.
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COVID-19 , Humanos , COVID-19/prevenção & controle , União Europeia , França , Alemanha , Suécia/epidemiologiaRESUMO
Many children and adolescents in Germany do not attend school regularly despite compulsory school attendance. Some of them only miss a few lessons, while others stay away from school for whole days, months or even years. The article shows how anxiety disorders can be the cause of school absenteeism and how this can be treated therapeutically.
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Absenteísmo , Transtornos de Ansiedade , Criança , Adolescente , Humanos , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/terapia , Instituições Acadêmicas , Alemanha/epidemiologiaRESUMO
Although negative effects of psychological interventions are suspected to be common, they are rarely investigated. Experts and international guidelines agree that monitoring for negative effects in clinical studies is needed to make psychological interventions safer and to empower patients before they give their consent to participate. Therefore, monitoring should already be considered during planning and preregistration of a study. The aim of this scoping review was to find out how frequently studies on psychological interventions monitor their negative effects according to preregistrations and to investigate reasons why monitoring is not carried out. Preregistrations of psychological interventions on ClinicalTrials.gov were scrutinized for information on monitoring of negative effects and other study characteristics. In a survey, researchers of studies where no monitoring was reported were asked for reasons for not doing so. Overall, 2231 preregistrations of psychological interventions were found; of these, only 3.4% included explicit information on monitoring for negative effects. In the survey, more researchers reported having conducted monitoring, although the type of monitoring was often inadequate. The type of monitoring varied widely, and specific monitoring measurements were rarely used repeatedly. Monitoring for negative effects was more prevalent in studies investigating treatments versus low-threshold interventions, in studies conducted in Europe versus other continents and in more recent studies. Researchers reported lack of knowledge as the most frequent reason for not monitoring negative effects. Our results imply a lack of monitoring and inconsistent information on negative effects in preregistrations, with inconsistent use of the term monitoring and measurements, and a lack of knowledge among researchers. Improved knowledge and a standardized approach, starting with an adequate preregistration, would be helpful to routinely examine negative effects in psychological interventions to make them safer and better.
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Depressão , Intervenção Psicossocial , Humanos , Depressão/terapia , Europa (Continente)RESUMO
BACKGROUND: Due to the high disease burden, the early onset and often long-term trajectories mental disorders are among the most widespread diseases with growing significance. The German Center for Mental Health (DZPG) was established to enhance research conditions and expedite the translation of clinically relevant findings into practice. OBJECTIVE: The aim of the DZPG is to optimize mental healthcare in Germany, influence modifiable social causes and to develop best practice models of care for vulnerable groups. It seeks to promote mental health and resilience, combat the stigmatization associated with mental disorders, and contribute to the enhancement of treatment across all age groups. MATERIAL AND METHODS: The DZPG employs a translational research program that accelerates the translation of basic research findings into clinical studies and general practice. University hospitals and outpatient departments, other university disciplines, and extramural research institutions are working together to establish a collaboratively coordinated infrastructure for accelerated translation and innovation. RESEARCH PRIORITIES: The research areas encompass 1) the interaction of somatic and mental risk and resilience factors and disorders across the lifespan, 2) influencing relevant modifiable environmental factors and 3) based on this personalized prevention and intervention. CONCLUSION: The DZPG aims to develop innovative preventive and therapeutic tools that enable an improvement in care for individuals with mental disorders. It involves a comprehensive integration of experts with experience at all levels of decision-making and employs trilogue and participatory approaches in all research projects.
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Transtornos Mentais , Resiliência Psicológica , Pesquisa Translacional Biomédica , Alemanha , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Transtornos Mentais/prevenção & controle , Humanos , Colaboração Intersetorial , Promoção da Saúde , Objetivos Organizacionais , Comunicação InterdisciplinarRESUMO
Little is known about toddlers' acquisition of specific emotion regulation (ER) strategies, and how early ER is shaped by temperament. This study investigated if 24-month-old German toddlers, predominantly from families with high levels of parental education (N = 96, n = 49 male), learned the ER strategy distraction through observational learning, and its interaction with temperament. Increased use of distraction correlated with reduced negative affect. Use of distraction increased through observational learning. Highly active toddlers tended to use active playing activities to distract themselves in a frustrating situation, whereas toddlers with a less active temperament used calmer activities. Toddlers' learning to apply distraction through observational learning was independent of a match between their own temperament and the model's actions.
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Regulação Emocional , Temperamento , Ira , Pré-Escolar , Emoções , Feminino , Humanos , Aprendizagem , MasculinoRESUMO
BACKGROUND: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. METHODS: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. RESULTS: Both treatments resulted in substantial improvements at post (PeEx-I: dwithin = 1.50, PeEx-S: dwithin = 1.78) and follow-up (PeEx-I: dwithin = 2.34; PeEx-S: dwithin = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TRPeEx-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. CONCLUSIONS: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.
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Terapia Implosiva , Qualidade de Vida , Ansiedade/terapia , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/terapia , Comorbidade , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Regarding the controversy about the overdiagnosis of Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents there are two main directions addressed as issue of age bias and issue of gender bias. In this relation, replication of findings demonstrating significant overdiagnosis is of importance which make the systematic evaluation of such occurrence necessary. OBJECTIVE: The seminal study by Bruchmüller, Margraf & Schneider, 2012 is replicated here, although in a different cultural context, in this case Iran, as ADHS might be perceived differently there. We assessed both gender bias and the impact of potential overdiagnosis on treatment recommendations. METHODS: A total of 344 licensed Iranian psychiatrists (mean age = 45.17, SD = 9.50) participated in this study. Each psychiatrist received a cover letter that introduced the study as well as a case vignette. Overall, there are eight different cases, one child with ADHD and three non-ADHD children, for both a boy (Ali) and a girl (Sara). Participants also received a questionnaire requesting their particular diagnosis, treatment recommendation and the therapist's sociodemographic information. Chi square tests and multiple logistic regression were applied for data analyses. RESULTS: Overdiagnosis occurred in both girl and boy children, although overdiagnosis was 2.45 more likely in boys than in girls (p < 0.01). With respect to the psychiatrist's gender, we detected no difference between males or females, as both overdiagnosed ADHD in boys (pfemale < 0.01 and pmale < 0.01). Furthermore, ADHD overdiagnosis had a direct impact on medication prescription (p < 0.01). CONCLUSION: This study suggests that diagnosticians should strictly adhere to diagnostic criteria to minimize diagnostic error.
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Transtorno do Deficit de Atenção com Hiperatividade , Psiquiatria , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Feminino , Humanos , Irã (Geográfico) , Masculino , Uso Excessivo dos Serviços de Saúde , Pessoa de Meia-Idade , SexismoRESUMO
Why do infants remember some things and not others? Human infants frequently cycle through different states such as calm attentiveness, wakeful activity, and crying. Given that cognitive processes do not occur in isolation, such fluctuations in internal state might influence memory processing. In the present experiment, declarative memory in 9-month-old infants (N = 96) was heavily state dependent. Infants exhibited excellent retention of a deferred imitation task after a 15-min delay if their state at encoding was identical to their state at retrieval (e.g., calm). Infants failed to exhibit retention if their state at encoding was different from their state at retrieval (e.g., calm vs. animated). Infant memory processing depends on internal cues.
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Desenvolvimento Infantil/fisiologia , Comportamento Imitativo/fisiologia , Comportamento do Lactente/fisiologia , Memória/fisiologia , Retenção Psicológica/fisiologia , Sinais (Psicologia) , Humanos , Lactente , Masculino , Rememoração Mental , Desempenho Psicomotor/fisiologiaRESUMO
Contrary to the well-documented link between parental and offspring clinical anxiety, little is known about the relationship between parental everyday-life anxieties (e.g., concerning family, finances, health) and offspring anxieties. To close this gap, we assessed the frequency of parental symptoms of DSM-IV anxiety disorders and everyday-life anxieties, as well as the frequency of offspring anxiety symptoms in a representative sample by self-report. Parents reported that 48.4% of the children were free of specific symptoms of DSM-IV anxiety disorders within the last 12 months, 39.2% showed low symptom load (1-3 symptoms) and 12.4% were moderately or severely strained (4-10 symptoms). Replicating previous studies, parental DSM-IV symptoms increased offspring risk for the same symptoms. In addition, parental everyday-life anxieties showed a positive relationship with offspring symptom severity. Demographic variables (female sex, low socioeconomic status and younger age) and parental anxiety markers explained 18% of variance in offspring symptom severity. The data are discussed in light of current models of familial transmission.
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Filho de Pais com Deficiência , Ansiedade , Transtornos de Ansiedade/diagnóstico , Medo , Feminino , Humanos , PaisRESUMO
Bullying experiences in outpatients of a child and adolescent psychotherapy centre - A particularly vulnerable group? Abstract. Objective: Bullying has both short- and long-term effects on physical and mental health. Thus, more victimized children might tend to be found in clinical samples. This is the first study to examine the prevalence of bullying roles and modes in children/adolescents in a psychotherapeutic outpatient setting in Germany. Method: 298 outpatients being treated in a child/adolescent psychotherapy centre (6-20 years, 50.7 % female) completed a questionnaire concerning their bullying experiences over the last 6 months. Results: 24.5 % of the patients reported from a victim's perspective, independent of being perpetrators of bullying. 19.1 % reported solely as victims, 5.4 % as victims who also bullied (bully-victims), and 2.0 % as bullies. More than one-third of those with victim or bully-victim experiences had been polyvictimized, 86.2 % were victims solely of traditional bullying, and 1.4 % solely of cyberbullying. The exploratory comparison to general-population school samples seems to show significantly more patients with victim experiences and significantly less patients who bullied others. There seem to be no significant effects for bully-victims. Compared to an inpatient sample, significantly fewer adolescent patients seem to state being victims or bully-victims. Conclusions: Bullying is a topic of particular importance in the context of psychotherapy. These findings have implications for the psychotherapeutic practice as well as training settings.
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Bullying/psicologia , Bullying/estatística & dados numéricos , Vítimas de Crime/psicologia , Vítimas de Crime/estatística & dados numéricos , Psicoterapia , Adolescente , Criança , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pacientes Ambulatoriais/psicologia , Pacientes Ambulatoriais/estatística & dados numéricosRESUMO
The nematode mutualistic bacterium Photorhabdus asymbiotica produces a large virulence-associated multifunctional protein toxin named PaTox. A glycosyltransferase domain and a deamidase domain of this large toxin function as effectors that specifically target host Rho GTPases and heterotrimeric G proteins, respectively. Modification of these intracellular regulators results in toxicity toward insects and mammalian cells. In this study, we identified a cysteine protease-like domain spanning PaTox residues 1844-2114 (PaToxP), upstream of these two effector domains and characterized by three conserved amino acid residues (Cys-1865, His-1955, and Asp-1975). We determined the crystal structure of the PaToxP C1865A variant by native single-wavelength anomalous diffraction of sulfur atoms (sulfur-SAD). At 2.0 Å resolution, this structure revealed a catalytic site typical for papain-like cysteine proteases, comprising a catalytic triad, oxyanion hole, and typical secondary structural elements. The PaToxP structure had highest similarity to that of the AvrPphB protease from Pseudomonas syringae classified as a C58-protease. Furthermore, we observed that PaToxP shares structural homology also with non-C58-cysteine proteases, deubiquitinases, and deamidases. Upon delivery into insect larvae, PaToxP alone without full-length PaTox had no toxic effects. Yet, PaToxP expression in mammalian cells was toxic and enhanced the apoptotic phenotype induced by PaTox in HeLa cells. We propose that PaToxP is a C58-like cysteine protease module that is essential for full PaTox activity.
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Toxinas Bacterianas/química , Cisteína Proteases/química , Photorhabdus/química , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Cristalografia por Raios X , Cisteína Proteases/genética , Cisteína Proteases/metabolismo , Photorhabdus/genética , Photorhabdus/metabolismo , Domínios ProteicosRESUMO
Assisting the Forgotten Ones - Interventions for Children of Parents with Psychological Disorders Mental diseases are associated with high levels of distress in various areas of life for those, who are affected. Taking a closer look at the social circumstances, not exclusively the people themselves but also their family members are affected, especially children. In adult treatment these children are often neglected, even if they have a higher risk of suffering a mental illness themselves. A huge amount of this risk is related to the special family environment children are often exposed to right after birth. We already find prevention programs helping these children and their parents to protect their mental health. These programs largely differ regarding parental psychopathology, setting or intensity. This article gives an overview of the special circumstances these children may be confronted with and hence derivates possible starting points to support affected families. A few existing programs will be described in detail. Empirical findings presented in the article give hope for the effectiveness of already existing programs and besides highlight the need for further research and changes in the care system.
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Filho de Pais com Deficiência/psicologia , Transtornos Mentais/prevenção & controle , Transtornos Mentais/terapia , Pais/psicologia , Adulto , Criança , Suscetibilidade a Doenças , Humanos , Transtornos Mentais/reabilitaçãoRESUMO
OBJECTIVE: Impairments in facial emotion recognition are an underlying factor of deficits in emotion regulation and interpersonal difficulties in mental disorders and are evident in eating disorders (EDs). METHODS: We used a computerized psychophysical paradigm to manipulate parametrically the quantity of signal in facial expressions of emotion (QUEST threshold seeking algorithm). This was used to measure emotion recognition in 308 adult women (anorexia nervosa [n = 61], bulimia nervosa [n = 58], healthy controls [n = 130], and mixed mental disorders [mixed, n = 59]). The M (SD) age was 22.84 (3.90) years. The aims were to establish recognition thresholds defining how much information a person needs to recognize a facial emotion expression and to identify deficits in EDs compared with healthy and clinical controls. The stimuli included six basic emotion expressions (fear, anger, disgust, happiness, sadness, surprise), plus a neutral expression. RESULTS: Happiness was discriminated at the lowest, fear at the highest threshold by all groups. There were no differences regarding thresholds between groups, except for the mixed and the bulimia nervosa group with respect to the expression of disgust (F(3,302) = 5.97, p = .001, η = .056). Emotional clarity, ED pathology, and depressive symptoms did not predict performance (RChange ≤ .010, F(1,305) ≤ 5.74, p ≥ .079). The confusion matrix did not reveal specific biases in either group. CONCLUSIONS: Overall, within-subject effects were as expected, whereas between-subject effects were marginal and psychopathology did not influence emotion recognition. Facial emotion recognition abilities in women experiencing EDs compared with women experiencing mixed mental disorders and healthy controls were similar. Although basic facial emotion recognition processes seems to be intact, dysfunctional aspects such as misinterpretation might be important in emotion regulation problems. CLINICAL TRIAL REGISTRATION NUMBER: DRKS-ID: DRKS00005709.
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Regulação Emocional , Expressão Facial , Reconhecimento Facial/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Percepção Social , Adolescente , Adulto , Feminino , Humanos , Adulto JovemRESUMO
In adults, sleep selectively consolidates those memories that are relevant for future events. The present study tested whether napping after encoding plays a role in selective memory consolidation in infants. Infants aged 15 and 24â months (nâ =â 48 per age) were randomly assigned to a nap or a no-nap demonstration condition, or a baseline control condition. In the demonstration conditions, infants observed an experimenter perform an irrelevant action followed by a relevant action to achieve a desirable outcome on four different toys. Infant imitation of irrelevant and relevant actions was coded at a test session that occurred after a 24-hr delay. The demonstration and test sessions were scheduled around infants' naturally occurring sleeping patterns. When order of actions was not taken into account, infants in both demonstration conditions exhibited retention of the relevant and irrelevant target actions. Contrary to expectations, infants in the nap condition did not perform the relevant action only more often than infants in the no-nap condition. As expected, only infants in the no-nap condition faithfully reproduced the two actions in the demonstrated order: irrelevant action first, followed by the relevant action. Thus, sleep might help infants to selectively "discard" aspects of a learning experience that they identify as being not useful or relevant in the future.