PBTK model-based analysis of CYP3A4 induction and the toxicokinetics of the pyrrolizidine alkaloid retrorsine in man.

Cytochrome P450 (CYP)3A4 induction by drugs and pesticides plays a critical role in the enhancement of pyrrolizidine alkaloid (PA) toxicity as it leads to increased formation of hepatotoxic dehydro-PA metabolites. Addressing the need for a quantitative analysis of this interaction, we developed a physiologically-based toxicokinetic (PBTK) model. Specifically, the model describes the impact of the well-characterized CYP3A4 inducer rifampicin on the kinetics of retrorsine, which is a prototypic PA and contaminant in herbal teas. Based on consumption data, the kinetics after daily intake of retrorsine were simulated with concomitant rifampicin treatment. Strongest impact on retrorsine kinetics (plasma AUC 24 and C max reduced to 67% and 74% compared to the rifampicin-free reference) was predicted directly after withdrawal of rifampicin. At this time point, the competitive inhibitory effect of rifampicin stopped, while CYP3A4 induction was still near its maximum. Due to the impacted metabolism kinetics, the cumulative formation of intestinal retrorsine CYP3A4 metabolites increased to 254% (from 10 to 25 nmol), while the cumulative formation of hepatic CYP3A4 metabolites was not affected (57 nmol). Return to baseline PA toxicokinetics was predicted 14 days after stop of a 14-day rifampicin treatment. In conclusion, the PBTK model showed to be a promising tool to assess the dynamic interplay of enzyme induction and toxification pathways.

A guide for a student-led doctoral-level qualitative methods short course in epidemiology: faculty and student perspectives.

Qualitative research and mixed methods are core competencies for epidemiologists. In response to the shortage of guidance on graduate course development, we wrote a course development guide aimed at faculty and students designing similar courses in epidemiology curricula. The guide combines established educational theory with faculty and student experiences from a recent introductory course for epidemiology and biostatistics doctoral students at the University of Zurich and Swiss Federal Institute of Technology, Zurich. We propose a student-centred course with inverse classroom teaching and practice exercises with faculty input. Integration of student input during the course development process helps align the course syllabus with student needs. The proposed course comprises six sessions that cover learning outcomes in comprehension, knowledge, application, analysis, synthesis and evaluation. Following an introductory session, the students engage in face-to-face interviews, focus group interviews, observational methods, analysis and how qualitative and quantitative methods are integrated in mixed methods. Furthermore, the course covers interviewer safety, research ethics, quality in qualitative research and a practice session focused on the use of interview hardware, including video and audio recorders. The student-led teaching characteristic of the course allows for an immersive and reflective teaching-learning environment. After implementation of the course and learning from faculty and student perspectives, we propose these additional foci: a student project to apply learned knowledge to a case study; integration in mixed-methods; and providing faculty a larger space to cover theory and field anecdotes.

PBTK modeling of the pyrrolizidine alkaloid retrorsine to predict liver toxicity in mouse and rat.

Retrorsine is a hepatotoxic pyrrolizidine alkaloid (PA) found in herbal supplements and medicines, food and livestock feed. Dose-response studies enabling the derivation of a point of departure including a benchmark dose for risk assessment of retrorsine in humans and animals are not available. Addressing this need, a physiologically based toxicokinetic (PBTK) model of retrorsine was developed for mouse and rat. Comprehensive characterization of retrorsine toxicokinetics revealed: both the fraction absorbed from the intestine (78%) and the fraction unbound in plasma (60%) are high, hepatic membrane permeation is dominated by active uptake and not by passive diffusion, liver metabolic clearance is 4-fold higher in rat compared to mouse and renal excretion contributes to 20% of the total clearance. The PBTK model was calibrated with kinetic data from available mouse and rat studies using maximum likelihood estimation. PBTK model evaluation showed convincing goodness-of-fit for hepatic retrorsine and retrorsine-derived DNA adducts. Furthermore, the developed model allowed to translate in vitro liver toxicity data of retrorsine to in vivo dose-response data. Resulting benchmark dose confidence intervals (mg/kg bodyweight) are 24.1-88.5 in mice and 79.9-104 in rats for acute liver toxicity after oral retrorsine intake. As the PBTK model was built to enable extrapolation to different species and other PA congeners, this integrative framework constitutes a flexible tool to address gaps in the risk assessment of PA.

Post-viral mental health sequelae in infected persons associated with COVID-19 and previous epidemics and pandemics: Systematic review and meta-analysis of prevalence estimates.

AIMS: Post-viral mental health problems (MHP) in COVID-19 patients and survivors were anticipated already during early stages of this pandemic. We aimed to synthesize the prevalence of the anxiety, depression, post-traumatic and general distress domain associated with virus epidemics since 2002. METHODS: In this systematic review and meta-analysis, we searched PubMed, PsycINFO, and Embase from 2002 to April 14, 2021 for peer-reviewed studies reporting prevalence of MHP in adults with laboratory-confirmed or suspected SARS-CoV-1, H1N1, MERS-CoV, H7N9, Ebolavirus, or SARS-CoV-2 infection. We included studies that assessed post-viral MHP with validated and frequently used scales. A three-level random-effects meta-analysis for dependent effect sizes was conducted to account for multiple outcome reporting. We pooled MHP across all domains and separately by severity (above mild or moderate-to-severe) and by acute (one month), ongoing (one to three months), and post-illness stages (longer than three months). A meta-regression was conducted to test for moderating effects, particularly for exploring estimate differences between SARS-Cov-2 and previous pandemics and epidemics. PROSPERO registration: CRD42020194535. RESULTS: We identified 59 studies including between 14 and 1002 participants and providing 187 prevalence estimates. MHP, in general, decreased from acute to post-illness from 46.3% to 38.8% and for mild and moderate-to-severe from 22.3% to 18.8%, respectively. We found no evidence of moderating effects except for non-random sampling and H1N1 showing higher prevalence. There was a non-significant trend towards lower MHP for SARS-CoV-2 compared to previous epidemics. CONCLUSIONS: MHP prevalence estimates decreased over time but were still on a substantial level at post-illness. Post-viral mental health problems caused by SARS-CoV-2 could have been expected much earlier, given the previous post-viral sequelae.

Relationship between Job Demands-Resources and turnover intention in chronic disease - The example of multiple sclerosis.

Considering the Job Demands-Resources (JD-R) model, this study investigated the relation between job demands, job resources and turnover intention among persons with multiple sclerosis (pwMS) as an example of chronic disease. We hypothesized that job demands and job resources are related to turnover intention, as mediated by work engagement, burnout, and MS-related work difficulties. Moreover, we assumed that MS-related work difficulties mediate the relationship between job demands/job resources and burnout and between job resources and work engagement. Using cross-sectional data (N = 360) of pwMS from the Swiss MS Registry, structural equation modelling was applied. The results confirm the JD-R model can be related to turnover intention among pwMS. Moreover, MS-related work difficulties mediated the relationship between job demands and burnout, between job resources and work engagement, and between job resources and burnout. The findings suggest that there may be benefit in applying and adapting the JD-R model for people with a chronic disease such as MS. This group of people might benefit from the promotion of job resources and a reduction in job demands, leading to changes in work engagement, burnout, and MS-related work difficulties and thus to an increased likelihood to stay at work.

Prevalence of Mental Health Problems During Virus Epidemics in the General Public, Health Care Workers and Survivors: A Rapid Review of the Evidence.

Background: The swift spread of SARS-CoV-2 provides a challenge worldwide. As a consequence of restrictive public health measures like isolation, quarantine, and community containment, the provision of mental health services is a major challenge. Evidence from past virus epidemics and the current SARS-CoV-2 outbreak indicate high prevalence rates of mental health problems (MHP) as short- and long-term consequences. However, a broader picture of MHP among different populations is still lacking. Methods: We conducted a rapid review on MHP prevalence rates published since 2000, during and after epidemics, including the general public, health care workers, and survivors. Any quantitative articles reporting on MHP rates were included. Out of 2,855 articles screened, a total of 74 were included in this review. Results: Most original studies on MHP were conducted in China in the context of SARS-CoV-1, and reported on anxiety, depression, post-traumatic stress symptoms/disorder, general psychiatric morbidity, and psychological symptoms. The MHP rates across studies, populations, and epidemics vary substantially. While some studies show high and persistent rates of MHP in populations directly affected by isolation, quarantine, threat of infection, infection, or life-threatening symptoms (e.g., health care workers), other studies report minor effects. Furthermore, even less affected populations (e.g., distant to epidemic epicenter, no contact history with suspected or confirmed cases) can show high rates of MHP. Discussion: MHP vary largely across countries and risk-groups in reviewed studies. The results call attention to potentially high MHP during epidemics. Individuals affected directly by an epidemic might be at a higher risk of short or even long-term mental health impairments. This study delivers insights stemming from a wide range of psychiatric instruments and questionnaires. The results call for the use of validated and standardized instruments, reference norms, and pre-post measurements to better understand the magnitude of the MHP during and after the epidemics. Nevertheless, emerging MHP should be considered during epidemics including the provision of access to mental health care to mitigate potential mental impairments.

Factors associated with employment and expected work retention among persons with multiple sclerosis: findings of a cross-sectional citizen science study.

BACKGROUND: Multiple sclerosis (MS) notably affects adults of working age. For persons with MS (PwMS), being employed enhances their quality of life and it may be regarded as an indicator of overall functioning. Thus, ensuring work participation in PwMS is of general public health interest. OBJECTIVE: To examine relevant socio-demographic, MS-, health- and work-related factors, including psychosocial working conditions, associated with currently working PwMS in Switzerland and their expected work retention. METHODS: Using cross-sectional data of PwMS in the Swiss MS Registry (n = 541, median age = 48 [IQR 40;55]), multivariable logistic regression models were computed. First, currently working PwMS were characterised in comparison with those not currently working. Second, expected work retention, operationalized as subjective judgement "likely to work in the same job in 2 years", was examined within the group of currently working PwMS. RESULTS: The factors age (OR 0.96, 95% CI 0.92-0.99), sex (OR 0.28, 95% CI 0.13-0.60), highest achieved job position (OR 1.21, 95% CI 1.01-1.46), health-related quality of life (HRQoL) (OR 1.02, 95% CI 1.01-1.04) and the number of MS symptoms (OR 0.90, 95% CI 0.82-0.98) were associated with currently working PwMS. Moreover, HRQoL (OR 1.07, 95% CI 1.04-1.10) and psychosocial working conditions, such as job resources (e.g. autonomy, control or social support) (OR 2.83, 95% CI 1.50-5.33) and job demands (e.g. workload, time pressure) (OR 0.41, 95% CI 0.18-0.90) were important factors for expected work retention among this group. CONCLUSIONS: Resourceful psychosocial working conditions are crucial for PwMS to maintain employment. Employers could contribute to work retention among PwMS by creating a work environment with resourceful psychosocial working conditions and providing, for instance, social support.

Capturing interprofessional collaboration between physicians and nurses in an acute care setting. A validation study of the revised German version of the Collaborative Practice Scales.

The relevance of interprofessional collaboration (IPC) is widely acknowledged. Given the lack of a fully validated instrument in the German language for measuring the level of IPC, we built upon the current, albeit psychometrically weak, German-language version of the instrument to devise a new version with improved wording and for subsequent psychometric testing. In a tertiary hospital in German-speaking Switzerland, 160 physicians and 374 nurses completed the revised Collaborative Practice Scales in German (CPS-G) and additional scales regarding positive and negative activation at work and regarding job demands and job resources. A confirmatory factor analysis of the CPS-G was performed, and internal consistency estimates were computed. Partial correlations between the CPS-G and the additional scales were examined for criterion validity. The model fit of the CPS-G was good for physicians (χ2/df = 2.38, p < .001; CFI = .923; RMSEA = .051, 90%-CI (0.037-0.065)) and moderate for nurses (χ2/df = 5, p < .001; CFI = .919; RMSEA = .087, 90%-CI (0.072-0.102)) supporting the two-factor structure of the original English version. Reliability was acceptable in all sub-scales for physicians (inclusion, α = 0.79; consensus, α = 0.80) and nurses (assertiveness, α = 0.77; understanding α = 0.82). As expected, the CPS-G physicians' subscales correlated positively with positive activation and job resources and negatively with negative activation and job demands, albeit not always statistically significantly. Similar correlations were found with the CPS-G nurses' subscales other than in one instance. The CPS-G showed good construct and criterion validity and acceptable internal consistency. It consequently represents a valid instrument ready for application to measure the level of interprofessional collaboration between nurses and physicians in acute care settings.

Report from the BfR expert hearing on practicability of hormonal measurements: recommendations for experimental design of toxicological studies with integrated hormonal end points.

This publication summarizes discussions that were held during an international expert hearing organized by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany, in October 2017. The expert hearing was dedicated to providing practical guidance for the measurement of circulating hormones in regulatory toxicology studies. Adequate measurements of circulating hormones have become more important given the regulatory requirement to assess the potential for endocrine disrupting properties for all substances covered by the plant protection products and biocidal products regulations in the European Union (EU). The main focus was the hypothalamus-pituitary-thyroid axis (HPT) and the hypothalamus-pituitary-gonadal axis (HPG). Insulin, insulin-like growth factor 1 (IGF-1), parathyroid hormone (PTH) and vitamins A and D were also discussed. During the hearing, the experts agreed on specific recommendations for design, conduct and evaluation of acceptability of studies measuring thyroid hormones, thyroid stimulating hormone and reproductive hormones as well as provided some recommendations for insulin and IGF-1. Experts concluded that hormonal measurements as part of the test guidelines (TGs) of the Organisation for Economic Co-operation and Development (OECD) were necessary on the condition that quality criteria to guarantee reliability and reproducibility of measurements are adhered to. Inclusion of the female reproductive hormones in OECD TGs was not recommended unless the design of the study was modified to appropriately measure hormone concentrations. The current report aims at promoting standardization of the experimental designs of hormonal assays to allow their integration in OECD TGs and highlights research needs for better identification of endocrine disruptors using hormone measurements.

Goal Pursuit in Organizational Health Interventions: The Role of Team Climate, Outcome Expectancy, and Implementation Intentions.

In taking a goal pursuit perspective into account, the present study examined associations between the context, process and outcome evaluation of an organizational health intervention (OHI) implemented within 29 teams in a hospital setting. In doing so, team climate for innovation as a context factor was measured at baseline (N = 529). Four to six weeks after baseline, N = 250 team representatives participated in a 4-day workshop. During the workshop employees formulated collective goals as action plans to be implemented in the nursing wards. Goal pursuit as a process factor was differentiated into (a) a motivational "goal setting" and (b) a volitional "goal striving" phase. The scale of outcome expectancy (measured after the fourth day of the workshop) was used as an indicator for the goal setting phase. For the operationalization of the goal striving phase, action plans were coded with regard to the proportion of formulated implementation intentions ("if-then plans"). After 6 months, the outcome of the intervention was measured on a retrospective impact scale (N = 385). The results of the multiple regression analysis and of the multilevel analysis show that both team climate and goal pursuit (outcome expectancy and the proportion of if-then plans) were positively related to the perceived impact of the intervention. Furthermore, the results show that the relationship between team climate and the impact of the intervention was mediated by outcome expectancy. The results highlight the contribution of goal theory within context-process-outcome research that leads to a better understanding of when and why OHIs are effective.

The influence of coercive measures on patients' stances towards psychiatric institutions.

OBJECTIVE: To examine the impact of coercive interventions (CI) on patients' evaluations of psychiatric hospitals as adversaries versus allies. METHODS: Self-constructed interviews were conducted relating to quantitative and subjective aspects of coercion and the attitude towards psychiatry of 79 patients with psychotic and bipolar disorders. The Coercion Experience Scale (CES) and the Admission Experience Survey (AES) were used to establish the subjective impact of CI. Instruments measuring psychopathological symptoms and the Global Assessment of Functioning (GAF) were applied alongside the Schedule for the Assessment of Illness (SAI) and the Beck Cognitive Insight Scale (BCIS). Using a logistic regression approach, considered influencing factors such as number, type and patients' subjective experiences of CI, cognitive and clinical insight, psychopathological symptoms and patients' global perceptions of their hospitalisation were analysed for their predictive value of patients' attitudes towards psychiatry. RESULTS: Binary logistic regression revealed that the subjective experience of CI and the perception of fairness and effectiveness during the treatment process predict patients' attitudes towards psychiatry to a greater extent than symptom-related measures or the quantity of CI. Patients presenting a higher degree of self-reflectiveness perceive psychiatric institutions more likely as allies. CONCLUSIONS: The manner in which coercion is subjectively experienced has direct influence on patients' perceptions of psychiatry.

[Coercive Interventions in Psychiatry: Prevention and Patients' Preferences]. / Psychiatrische Zwangsmaßnahmen: Prävention und Präferenzen aus Patientenperspektive.

Objective This study explores patients' preferences and measures of prevention of coercive methods in psychiatric treatment. Methods Structured interviews of 90 patients with psychotic disorders were undertaken, most of whom had previously experienced coercive methods. Results Participants saw preventive potential in a wider availability of individual non-pharmacological therapy, improvement of staff professional competence and communication skills, high staff-to-patient ratios and retreat facilities. The majority of participants preferred forced medication and manual restraint in case of self-endangerment, and forced medication and mechanical restraint in the event of endangerment of others. Conclusion Patients' suggestions relating to prevention of coercion are in line with most expert's opinions. In case coercive methods are required, manual restraint and application of forced medication is accepted as the treatment of choice according to most patients in case of self-endangerment.

Subjective experience of emotions and emotional empathy in paranoid schizophrenia.

Unlike the cognitive dimensions, alterations of the affective components of empathy in schizophrenia are less well understood. This study explored cognitive and affective dimensions of empathy in the context of the subjective experience of aspects of emotion processing, including emotion regulation, emotional contagion, and interpersonal distress, in individuals with schizophrenia and healthy controls. In addition, the predictive value of these parameters on psychosocial function was investigated. Fifty-five patients with paranoid schizophrenia and 55 healthy controls were investigated using the Multifaceted Empathy Test and Interpersonal Reactivity Index, as well as the Subjective Experience of Emotions and Emotional Contagion Scales. Individuals with schizophrenia showed impairments of cognitive empathy, but maintained emotional empathy. They reported significantly more negative emotional contagion, overwhelming emotions, lack of emotions, and symbolization of emotions by imagination, but less self-control of emotional expression than healthy persons. Besides cognitive empathy, the experience of a higher extent of overwhelming emotions and of less interpersonal distress predicted psychosocial function in patients. People with schizophrenia and healthy controls showed diverging patterns of how cognitive and emotional empathy related to the subjective aspects of emotion processing. It can be assumed that variables of emotion processing are important moderators of empathic abilities in schizophrenia.

The contribution of thioredoxin-2 reductase and glutathione peroxidase to H(2)O(2) detoxification of rat brain mitochondria.

Brain mitochondria are not only major producers of reactive oxygen species but they also considerably contribute to the removal of toxic hydrogen peroxide by the glutathione (GSH) and thioredoxin-2 (Trx2) antioxidant systems. In this work we estimated the relative contribution of both systems and catalase to the removal of intrinsically produced hydrogen peroxide (H(2)O(2)) by rat brain mitochondria. By using the specific inhibitors auranofin and 1-chloro-2,4-dinitrobenzene (DNCB), the contribution of Trx2- and GSH-systems to reactive oxygen species (ROS) detoxification in rat brain mitochondria was determined to be 60±20% and 20±15%, respectively. Catalase contributed to a non-significant extent only, as revealed by aminotriazole inhibition. In digitonin-treated rat hippocampal homogenates inhibition of Trx2- and GSH-systems affected mitochondrial hydrogen peroxide production rates to a much higher extent than the endogenous extramitochondrial hydrogen peroxide production, pointing to a strong compartmentation of ROS metabolism. Imaging experiments of hippocampal slice cultures showed on single cell level substantial heterogeneity of hydrogen peroxide detoxification reactions. The strongest effects of inhibition of hydrogen peroxide removal by auranofin or DNCB were detected in putative interneurons and microglial cells, while pyramidal cells and astrocytes showed lower effects. Thus, our data underline the important contribution of the Trx2-system to hydrogen peroxide detoxification in rat hippocampus. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

Aggressive behavior and measurement of psychopathy in female inmates of German prisons--a preliminary study.

Studies concerning inmate psychopathy (as measured by Psychopathy-Checklist-Revised, PCL-R; Hare, 1991) have predominantly been concerned with male inmates. This study was the first to look into psychopathy using the PCL-R with the whole required procedure in German prisons with female inmates. The aims of the present study were to gain data about the prevalence of psychopathy in this sample and to examine potential relations between the types and motive of aggression, prosocial behavior and scores on the PCL-R. Sixty female inmates were examined. We obtained a prevalence rate of psychopathy of 17% (N=10, with a cut-off score of 25). Considering a wide range of subtypes of aggressive behaviors, we found that physical proactive, and relational reactive aggression as well as age predicted high scores of psychopathy. However, prosocial or helping behavior was not associated with psychopathy. Implications for diagnostic issues in forensics concerning female prisoners are discussed.

Association between oxytocin receptor gene polymorphisms and self-rated 'empathic concern' in schizophrenia.

The nonapeptide oxytocin (OXT) and its receptor (OXTR) have been implicated in social cognition, empathy, emotion and stress regulation in humans. Previous studies reported associations between OXT and OXTR genetic polymorphisms and risk for disorders characterized by impaired socio-emotional functioning, such as schizophrenia and autism. Here we investigate the influence of two single nucleotide polymorphisms (SNPs) within the OXTR gene on a measure of socio-emotional functioning in schizophrenic patients. OXTR SNPs that were previously investigated in other studies were genotyped in 145 patients diagnosed with schizophrenia according to DSM-IV and 145 healthy controls matched for age and gender. The Interpersonal Reactivity Index (IRI) was used to assess cognitive ('perspective taking'), affective ('empathic concern') and self-related ('personal distress') dimensions of empathy. No group differences in genotype frequencies were observed. MANCOVA revealed a significant main (F [1,282] = 10.464; p<0.01) and interaction effect (genotype by diagnosis: F [1,282] = 4.329; p<0.05) of OXTR SNP rs2254298(A>GG) with 'empathic concern'. Within the schizophrenia group, linear regression analysis determined OXTR rs2254298 genotype, PANSS negative and general symptom score, and age of disease onset as being significantly associated with 'empathic concern'. OXTR rs2254298 significantly impacted PANSS general psychopathology scores. No associations were found for OXTR rs53576, IRI 'perspective taking' or 'personal distress' ratings. Our preliminary findings support hypotheses about an involvement of OXTR rs2254298 in emotional empathy in schizophrenic and healthy individuals, warranting independent replication.

Subtle deficits of cognitive theory of mind in unaffected first-degree relatives of schizophrenia patients.

Alterations of theory of mind (ToM) and empathy were implicated in the formation of psychotic experiences, and deficits in psychosocial functioning of schizophrenia patients. Inspired by concepts of neurocognitive endophenotypes, the existence of a distinct, potentially neurobiologically based social-cognitive vulnerability marker for schizophrenia is a matter of ongoing debate. The fact that previous research on social-cognitive deficits in individuals at risk yielded contradictory results may partly be due to an insufficient differentiation between qualitative aspects of ToM. Thirty-four unaffected first-degree relatives of schizophrenia patients (21 parents, 8 siblings, 5 children; f/m: 30/4; mean age: 48.1 ± 12.7 years) and 34 controls subjects (f/m: 25/9; mean age: 45.9 ± 10.9 years) completed the 'Movie for the Assessment of Social Cognition'-a video-based ToM test-and an empathy questionnaire (Interpersonal Reactivity Index, IRI). Outcome parameters comprised (1) 'cognitive' versus 'emotional' ToM, (2) error counts representing 'undermentalizing' versus 'overmentalizing', (3) empathic abilities and (4) non-social neurocognition. MANCOVA showed impairments in cognitive but not emotional ToM in the relatives' group, when age, gender and neurocognition were controlled for. Relatives showed elevated error counts for 'undermentalizing' but not for 'overmentalizing'. No alterations were detected in self-rated dimensions of empathy. Of all measures of ToM and empathy, only the IRI subscale 'fantasy' was associated with measures of psychotic risk, i.e. a history of subclinical delusional ideation. The present study confirmed subtle deficits in cognitive, but not emotional ToM in first-degree relatives of schizophrenia patients, which were not explained by global cognitive deficits. Findings corroborate the assumption of distinct social-cognitive abilities as an intermediate phenotype for schizophrenia.

Subjective underchallenge at work and its impact on mental health.

PURPOSE: To investigate the relation between subjective underchallenge at work and the degree of depressiveness and life satisfaction. METHODS: A representative sample of the German general population of N = 1,178 (52.5% men; age: M = 40.4 years, SD = 11.3) was included in this study. Measurements contain Satisfaction with Life Scalè (SWLS) and the Patient Health Questionnairè (PHQ-D). To assess subjective underchallenge at work, a ten-item scale was developed for the purpose of this study. The association between subjective underchallenge at work, life satisfaction and depressiveness was examined by means of path analyses. RESULTS: A significant positive association was found between subjective underchallenge at work and depressiveness, mediated by life satisfaction. This association was not moderated by income but by level of education. Participants with a medium educational level displayed a weaker association than participants with either a high or a low educational level. CONCLUSION: Not only work overload but also feeling underchallenged at work can have a negative impact on mental health and well-being. This is not an issue for blue-collar workers only and deserves more attention in future research.

Different aspects of theory of mind in paranoid schizophrenia: evidence from a video-based assessment.

In schizophrenia, impairments of theory of mind (ToM) may be due to excessive ('overmentalizing') or defective ('undermentalizing') attribution of mental states. However, most ToM tests differentiate neither between 'overmentalizing' and 'undermentalizing' nor between cognitive and affective ToM in schizophrenia. This study aimed at differentiating these aspects of ToM in 80 patients diagnosed with paranoid schizophrenia and 80 matched healthy controls using the 'Movie for the Assessment of Social Cognition' (MASC). Outcome parameters comprised 1) error counts representing 'undermentalizing' or 'overmentalizing', 2) decoding of cognitive or emotional mental states and 3) non-social inferencing. Multivariate analysis of covariance (MANCOVA) showed significantly abnormal scores for two dimensions of 'undermentalizing' as well as for cognitive and emotional ToM that were not explained by global cognitive deficits. Scores for 'overmentalizing' did not differ between groups, when age, gender, non-social reasoning and memory were controlled. In schizophrenic patients, negative symptoms were associated with a lack of a mental state concept, while positive symptoms like delusions were associated with 'overmentalizing', supporting respective etiological concepts of delusions.

Investigation of the fluorolysis of magnesium methoxide.

The structures of magnesium methoxide and magnesium methoxide fluoride obtained via the reaction of Mg(OCH(3))(2) with HF were investigated by single-crystal structure analysis and multinuclear solid-state NMR ((13)C and (19)F). The fluorolysis of magnesium methoxide transforms the cubane structure units in hexanuclear dicubane units containing micro(4)-fluorine atoms. The resulting Mg(6)F(2)(OCH(3))(10)(CH(3)OH)(14) compound crystallizes in two different crystalline modifications. Moreover by slow thermal decomposition of the compound Mg(6)F(2)(OCH(3))(10)(CH(3)OH)(14), it loses two outer CH(3)OH molecules and leaves crystal structure Mg(6)F(2)(OCH(3))(10)(CH(3)OH)(12). The thermal behavior of Mg(OCH(3))(2)(CH(3)OH)(3.55) and Mg(6)F(2)(OCH(3))(10)(CH(3)OH)(14) was investigated by DTA and XRD. Both compounds lose the solvated methanol completely by heating above 150 degrees C and form MgO above 600 degrees C as well as amorphous MgF(2) in the case of magnesium methoxide fluoride.