Determinants of patient-reported outcome trajectories and symptomatic recovery in Improving Access to Psychological Therapies (IAPT) services.

BACKGROUND: Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting. METHODS: Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery. RESULTS: Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria). CONCLUSIONS: We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients' needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.

Mood and neural responses to social rejection do not seem to be altered in resilient adolescents with a history of adversity.

Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered "resilient"), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.

Gait and strength assessment following surgical repair by intramedullary nailing of isolated tibial shaft fracture.

The objective of the study was to evaluate the long-term strength and gait outcomes after intramedullary nailing of isolated tibial diaphyseal fractures. This retrospective cohort study was conducted at an academic Level I trauma center. Fifteen participants with isolated tibial diaphyseal fractures (OTA/AO 42) at least 2 years postoperative from intramedullary nailing (IMN) provided informed consent. The average age was 40 ± 14 (range, 24-69); there were nine men and six women. Knee flexion-extension strength data were collected. Temporal-spatial, kinematic, and kinetic gait parameters were measured and compared to historic control data. Participants completed the SF-36 and shortened musculoskeletal function assessment questionnaires. The mean length of follow-up between surgery and gait analysis was 6 ± 2 years. The fractured limb demonstrated deficits in quadriceps strength between 9.8% and 23.4% compared to the unaffected limb. Temporal-spatial parameters revealed slower walking speed, shorter stride length, decreased cadence, and shorter single-limb support time in the fractured limb. Altered kinematic and kinetic findings included a knee extension shift during stance, with an increased knee flexor moment demand and decreased total knee power during loading and midstance. These findings represent deficits in concentric and eccentric knee extensor activity. Additionally, the fractured limb demonstrated decreased ankle dorsiflexion during stance and diminished ankle push-off power. Long-term outcomes after IMN of tibial diaphyseal fractures demonstrate decreased quadriceps strength and altered gait parameters that may have implications to the high incidence of knee and ankle pain in the fractured limb.

The Comprehensive Adversity Measure (CAM): A measure of early adversity and its severity.

BACKGROUND: Early adversity scales often display insufficient content coverage and typically assess the presence of adversity, but not its severity. OBJECTIVE: To address some of these limitations, we developed the 13-item Youth and Childhood Adversity Scale. We subsequently revised and expanded the scale regarding content coverage and item wording, resulting in a 22-item version, which we here describe. METHODS: We conducted one cross-sectional (N = 1498; 43.9 % females; 24.42 years, SD = 3.72, range: 18-30 years) and one longitudinal study (N = 1084; 39.6 % females; 32 years, SD = 10.49, range: 18-75 years). To reflect the nature of the revised measure more accurately, it was named the Comprehensive Adversity Measure (CAM). RESULTS: Exploratory factor analysis suggested a one-factor model for both the presence/absence and the severity facet, which both displayed good model fit in subsequent confirmatory factor analyses. Factor models demonstrated at least scalar measurement invariance across gender and country (US/UK). Correlations with psychological distress, depression, anxiety, substance use, posttraumatic stress symptoms, obsessive-compulsive symptoms, suicide attempts, rumination, social comparison, self-esteem, and quality of life provided evidence in support of construct validity - concurrently and prospectively. CONCLUSIONS: The CAM offers a psychometrically-sound, content-wise comprehensive, and free to use assessment of early adversity.

A Cross-Country Network Analysis of Resilience Systems in Young Adults.

Multisystemic resilience has been conceptualised as involving a constellation of protective factors which operate at different levels to promote adaptation and thriving despite experiences of adversity. We used network modelling to discover how protective factors at two different systemic levels (intrapersonal strengths and social-ecological resources) interrelate, drawing on survey data from 5283 emerging adults (M = 24.53 years; 52% female) in Brazil, China, Indonesia, Russia, Thailand, the US and Vietnam. Results indicated that the level of connectivity within and between protective factor levels was similar between the countries, but that there was substantial variation in the specific interrelations among protective factors (both within and between levels), including the presence of some country-specific negative interrelations between protective factors at different levels. The findings support the importance of cultural context in studies of resilience, with implications for the development of appropriate resilience-building interventions for this age group.

Analysis of Protective Factors in Schoolchildren in England Using the Dual-factor Model of Mental Health.

The dual-factor approach to mental health was employed to explore levels and interrelations of protective factors associated with resilience in a dataset of 30,841 schoolchildren aged 11-14 in England. ANOVA was used to contrast levels of protective factors between groups (combinations of higher/lower psychopathology and higher/lower wellbeing) and network analysis to explore protective factor interrelations. Levels of protective factors tended to be highest for those who had higher wellbeing and lower psychopathology (termed 'complete mental health'). Those with lower levels of protective factors were split between two subpopulations: having lower wellbeing and higher psychopathology (termed 'troubled'), and having lower wellbeing and lower psychopathology (termed 'vulnerable'). Analysis of the protective factor networks revealed that the four subpopulations of the model were distinguished by both their overall structure and individual node connectivity (the 'complete mental health' subpopulation demonstrated the greatest connectivity), though two were similar: those with higher wellbeing and higher psychopathology (termed 'symptomatic but content') and lower wellbeing and higher psychopathology ('troubled'). The results indicate that while 'vulnerable' and 'symptomatic but content' may be hard to discriminate conceptually, the former may reflect a lower capacity to cope during periods of adversity (i.e., show resilience). Overall, the results encourage a holistic approach to mental health screening, particularly as children with lower wellbeing had lower levels of the protective factors, regardless of their level of psychopathology. Moreover, interventions to improve protective factors associated with positive development in stressed environments may therefore have a greater impact on improving wellbeing than decreasing symptoms of psychopathology.

Networks of Adversity in Childhood and Adolescence and Their Relationship to Adult Mental Health.

Adverse experiences before the age of eighteen are common and include diverse events ranging from sexual abuse to parental divorce. These stressful experiences have been linked to physical and mental health issues. Previous research has focused mainly on childhood adversity, such as experiences in the family environment. Little consideration has been given to adversities that may be particularly harmful in adolescence. To understand adolescents' adverse experiences, this project used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, total N = 14,901, N ≈ 1,200 - 10,000 per measure). We modelled interrelations of adversities in childhood (1-11 years) and adolescence (11-23 years) and examined adversity clusters using network analysis. We found two similar clusters in the childhood and adolescence networks: (1) direct abuse and (2) adverse family factors. We identified a third cluster of (3) educational and social adversities for adolescence. For both age groups, emotional abuse in the family environment was closely linked to mental health in early adulthood and most adversities were linked with depression in early adulthood. In adolescence, housing and academic issues and abuse by a romantic partner were particularly central to the network of adversities. Thus, we found commonalities and differences in the relevance of adverse experiences at different developmental stages. These findings highlight the need to develop age-dependent frameworks for adversity research and policymaking.

Running to the beat: Does listening to music affect running cadence and lower extremity biomechanics?

BACKGROUND: Gait retraining can be effective in altering lower extremity biomechanics and reducing risk of injury. In attempts to alter running gait, previous studies used metronomes to manipulate cadence. RESEARCH QUESTION: The aim of this study was to determine if manipulating running cadence via music could alter lower extremity biomechanics. METHODS: Eighteen runners ran at a self-selected speed (SS) and ran to music where the beats per minute (bpm) of the songs was increased by 5% (+5%) and 10% (+10%). Kinematic and kinetic data were collected with a motion capture system and a triaxial accelerometer. A one-way repeated measures analysis of variance (ANOVA) was applied to test the effect of bpm (SS, +5%, +10%) on cadence, heart rate and peak vertical acceleration. A statistical parametric mapping (SPM) one-way repeated measures ANOVA was used to test the effect of bpm on the sagittal plane kinematic signals during stance phase. RESULTS: There was a significant main effect for bpm on the discrete metrics. Post hoc tests showed significant differences in heartrate from SS to + 5%, + 5% to + 10%, and SS to 10%. There were no significant differences between cadence or peak acceleration. SIGNIFICANCE: In the current study, listening to music with faster bpm was not shown to increase cadence and decrease peak tibial accelerations during running.

Interrelations of resilience factors and their incremental impact for mental health: insights from network modeling using a prospective study across seven timepoints.

Resilience can be viewed as trajectory of stable good mental health or the quick recovery of mental health during or after stressor exposure. Resilience factors (RFs) are psychological resources that buffer the potentially negative effects of stress on mental health. A problem of resilience research is the large number of conceptually overlapping RFs complicating their understanding. The current study sheds light on the interrelations of RFs in the face of the COVID-19 pandemic as a use case for major disruptions. The non-preregistered prospective study assessed a sample of 1275 German-speaking people from February 2020 to March 2021 at seven timepoints. We measured coping, hardiness, control beliefs, optimism, self-efficacy, sense of coherence (SOC), sense of mastery, social support and dispositional resilience as RFs in February 2020, and mental health (i.e., psychopathological symptoms, COVID-19-related rumination, stress-related growth) at all timepoints. Analyses used partial correlation network models and latent growth mixture modeling (LGMM). Pre-pandemic RFs were strongly interrelated, with SOC being the most central node. The strongest associations emerged between coping using emotional support and social support, SOC and sense of mastery, and dispositional resilience and self-efficacy. SOC and active coping were negatively linked. When we examined RFs as predictors of mental health trajectories, SOC was the strongest predictor of psychopathological symptoms and rumination, while trajectories of stress-related growth were predicted by optimism. Subsequent network analyses, including individual intercepts and slopes from LGMM, showed that RFs had small to moderate associations with intercepts but were unrelated to slopes. Our findings provide evidence for SOC playing an important role in mental distress and suggest further examining SOC's incremental validity. However, our results also propose that RFs might be more important for stable levels of mental health than for adaptation processes over time. The differential associations for negative and positive outcomes support the use of multidimensional outcomes in resilience research.

Impact of Internal Malrotation of the Femur Followed by Derotational Osteotomy as Demonstrated by 3D Gait Analysis: A Case Report.

CASE: An 18-year-old man with 48° of internal malrotation of the femur after nailing underwent derotational osteotomy with gait dynamics and electromyography data collected preoperatively and postoperatively. Hip abduction and internal foot progression angles were significantly deviated from normal preoperatively compared with the contralateral side. At 10 months postoperatively, the hip was abducted and externally rotated throughout the entire gait cycle. His Trendelenburg gait had resolved, and he reported no residual functional concerns. Before corrective osteotomy, walking velocity was significantly slower with shorter stride lengths. CONCLUSION: Significant internal malrotation of the femur impairs hip abduction and foot progression angles as well as gluteus medius activation during ambulation. Derotational osteotomy considerably corrected these values.

On Dimensionality, Measurement Invariance, and Suitability of Sum Scores for the PHQ-9 and the GAD-7.

In psychiatry, severity of mental health conditions and their change over time are usually measured via sum scores of items on psychometric scales. However, inferences from such scores can be biased if psychometric properties such as unidimensionality and temporal measurement invariance for instruments are not met. Here, we aimed to evaluate these properties for common measures of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder Assessment-7) in a large clinical sample (N = 22,362) undergoing psychotherapy. In addition, we tested consistency in dimensionality results across different methods (parallel analysis, factor analysis, explained common variance, the partial credit model, and the Mokken model). Results showed that while both Patient Health Questionnaire-9 and Generalized Anxiety Disorder Assessment-7 are multidimensional instruments with highly correlated factors, there is justification for sum scores as measures of severity. Temporal measurement invariance across 10 therapy sessions was evaluated. Strict temporal measurement invariance was established in both scales, allowing researchers to compare sum scores as severity measures across time.

The impact of the initial COVID-19 outbreak on young adults' mental health: a longitudinal study of risk and resilience factors.

Few studies assessing the effects of COVID-19 on mental health include prospective markers of risk and resilience necessary to understand and mitigate the combined impacts of the pandemic, lockdowns, and other societal responses. This population-based study of young adults includes individuals from the Neuroscience in Psychiatry Network (n = 2403) recruited from English primary care services and schools in 2012-2013 when aged 14-24. Participants were followed up three times thereafter, most recently during the initial outbreak of the COVID-19 outbreak when they were aged between 19 and 34. Repeated measures of psychological distress (K6) and mental wellbeing (SWEMWBS) were supplemented at the latest assessment by clinical measures of depression (PHQ-9) and anxiety (GAD-7). A total of 1000 participants, 42% of the original cohort, returned to take part in the COVID-19 follow-up; 737 completed all four assessments [mean age (SD), 25.6 (3.2) years; 65.4% female; 79.1% White]. Our findings show that the pandemic led to pronounced deviations from existing mental health-related trajectories compared to expected levels over approximately seven years. About three-in-ten young adults reported clinically significant depression (28.8%) or anxiety (27.6%) under current NHS guidelines; two-in-ten met clinical cut-offs for both. About 9% reported levels of psychological distress likely to be associated with serious functional impairments that substantially interfere with major life activities; an increase by 3% compared to pre-pandemic levels. Deviations from personal trajectories were not necessarily restricted to conventional risk factors; however, individuals with pre-existing health conditions suffered disproportionately during the initial outbreak of the COVID-19 pandemic. Resilience factors known to support mental health, particularly in response to adverse events, were at best mildly protective of individual psychological responses to the pandemic. Our findings underline the importance of monitoring the long-term effects of the ongoing pandemic on young adults' mental health, an age group at particular risk for the emergence of psychopathologies. Our findings further suggest that maintaining access to mental health care services during future waves, or potential new pandemics, is particularly crucial for those with pre-existing health conditions. Even though resilience factors known to support mental health were only mildly protective during the initial outbreak of the COVID-19 pandemic, it remains to be seen whether these factors facilitate mental health in the long term.

Multi-segment foot kinematics during gait following ankle arthroplasty.

Ankle arthritis is a debilitating disease marked by pain and limited function. Total ankle arthroplasty improves pain while preserving motion and offers an alternative to the traditional treatment of ankle fusion. Gait analysis and functional outcomes tools can provide an objective balanced analysis of ankle replacement for the treatment of ankle arthritis. Twenty-nine patients with end-stage ankle arthritis were evaluated before and after ankle arthroplasty. Multi-segment foot and ankle kinematics were assessed annually following surgery (average 3.5 years, range 1-6 years) using the Milwaukee Foot Model and a Vicon video motion analysis system. Functional outcomes (American Orthopedic Foot and Ankle Society [AOFAS] ankle/hindfoot scale, short form 36 [SF-36] questionnaire) and temporal-spatial parameters were also assessed. Kinematic results were compared to findings from a previously collected group of healthy ambulators. AOFAS and SF-36 mean scores improved postoperatively. Walking speed and stride length increased after surgery. There were significant improvements in tibial sagittal range of motion in terminal stance and hindfoot sagittal range of motion in preswing. Decreased external rotation of the tibia and increased external rotation of the hindfoot were noted throughout the gait cycle. Pain and function improved after ankle replacement as supported by better outcomes scores, increased temporal-spatial parameters, and significant improvement in tibial sagittal range of motion during terminal stance and hindfoot sagittal range of motion during preswing. While multi-segment foot kinematics were improved, they were not restored to control values. Statement of clinical significance: Total ankle arthroplasty does not fully normalize mutli-segment gait kinematics despite improved patient-reported outcomes and gait mechanics.

The Youth and Childhood Adversity Scale: a step towards developing a new measure of adversity and its severity.

Background: Early adversity (EA) can contribute to the onset, manifestation, and course of various mental disorders. Measuring EA is still conceptually and psychometrically challenging due to issues such as content coverage, item-wording, scaling methods, and validation procedures. Further, despite research demonstrating the importance of the severity of EA, most EA scales solely focused on the 'presence-versus-absence' indicator of adverse events.Objective: To address these potentially relevant gaps, we have developed a 13-item measure of EA, the Youth and Childhood Adversity Scale (YCAS). Beyond a dichotomous assessment of whether a set of adverse events have been experienced, this scale also assesses the respective severity of these events.Methods: We evaluated the YCAS in a sample of 596 adolescent students (ages 16-19) and a second sample of 451 medical students (ages 18-30+). Exploratory factor analysis was used to determine the underlying structure as proposed by the data, which was then tested with confirmatory factor analysis. We psychometrically assessed both factor scores and sum scores.Results: In both samples, a one-factorial solution was found for both responses to dichotomous items and severity items. Item loadings had a broad range, with minimum loadings of .1-.2 and maximum loadings of .7-.9. Irrespective of the response type, this factor exhibited good reliability (omega total, range: .80 - .89) and was associated with a range of mental-health outcomes, self-esteem, and childhood maltreatment. The fit of the model resembling sum scores was not satisfactory, but the sum score reliability (coefficient alpha, range: .78 - .89) was acceptable and most of the associations with the validation measures held.Conclusions: The YCAS allows an efficient, reliable, and valid assessment of EA and its severity. It covers a reasonable breadth of events, whilst simultaneously being parsimonious. We discuss next steps of how to improve this measure to fully capture the complexity of EA.

We present the Youth and Childhood Adversity Scale (YCAS), measuring the presence and severity of adversities.Both yes/no and severity ratings had a 1-factor solution of good reliability and validity.Further refinement of the YCAS, eg improved content breadth, is suggested.

Tracking Stress, Mental Health, and Resilience Factors in Medical Students Before, During, and After a Stress-Inducing Exam Period: Protocol and Proof-of-Principle Analyses for the RESIST Cohort Study.

BACKGROUND: Knowledge of mental distress and resilience factors over the time span from before to after a stressor is important to be able to leverage the most promising resilience factors and promote mental health at the right time. To shed light on this topic, we designed the RESIST (Resilience Study) study, in which we assessed medical students before, during, and after their yearly exam period. Exam time is generally a period of notable stress among medical students, and it has been suggested that exam time triggers mental distress. OBJECTIVE: In this paper, we aim to describe the study protocol and to examine whether the exam period indeed induces higher perceived stress and mental distress. We also aim to explore whether perceived stress and mental distress coevolve in response to exams. METHODS: RESIST is a cohort study in which exam stress functions as a within-subject natural stress manipulation. In this paper, we outline the sample (N=451), procedure, assessed measures (including demographics, perceived stress, mental distress, 13 resilience factors, and adversity), and ethical considerations. Moreover, we conducted a series of latent growth models and bivariate latent change score models to analyze perceived stress and mental distress changes over the 3 time points. RESULTS: We found that perceived stress and mental distress increased from the time before the exams to the exam period and decreased after the exams to a lower level than before the exams. Our findings further suggest that higher mental distress before exams increased the risk of developing more perceived stress during exams. Higher perceived stress during exams, in turn, increased the risk of experiencing a less successful (or quick) recovery of mental distress after exams. CONCLUSIONS: As expected, the exam period caused a temporary increase in perceived stress and mental distress. Therefore, the RESIST study lends itself well to exploring resilience factors in response to naturally occurring exam stress. Such knowledge will eventually help researchers to find out which resilience factors lend themselves best as prevention targets and which lend themselves best as treatment targets for the mitigation of mental health problems that are triggered or accelerated by natural exam stress. The findings from the RESIST study may therefore inform student support services, mental health services, and resilience theory.

Psychological Network Analysis of General Self-Efficacy in High vs. Low Resilient Functioning Healthy Adults.

Resilience to stress has gained increasing interest by researchers from the field of mental health and illness and some recent studies have investigated resilience from a network perspective. General self-efficacy constitutes an important resilience factor. High levels of self-efficacy have shown to promote resilience by serving as a stress buffer. However, little is known about the role of network connectivity of self-efficacy in the context of stress resilience. The present study aims at filling this gap by using psychological network analysis to study self-efficacy and resilience. Based on individual resilient functioning scores, we divided a sample of 875 mentally healthy adults into a high and low resilient functioning group. To compute these scores, we applied a novel approach based on Partial Least Squares Regression on self-reported stress and mental health measures. Separately for both groups, we then estimated regularized partial correlation networks of a ten-item self-efficacy questionnaire. We compared three different global connectivity measures-strength, expected influence, and shortest path length-as well as absolute levels of self-efficacy between the groups. Our results supported our hypothesis that stronger network connectivity of self-efficacy would be present in the highly resilient functioning group compared to the low resilient functioning group. In addition, the former showed higher absolute levels of general self-efficacy. Future research could consider using partial least squares regression to quantify resilient functioning to stress and to study the association between network connectivity and resilient functioning in other resilience factors.

Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons.

The anthocyanidin delphinidin (DEL) has recently been shown to inhibit human topoisomerase I and II, without stabilizing the covalent DNA/topoisomerase intermediate [Habermeyer, M., Fritz, J., Barthelmes, H. U., Christensen, M. O., Larsen, M. K., Boege, F., and Marko, D. (2005) Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity. Chem. Res. Toxicol. 18, 1395-404]. In the present study, we demonstrated that DEL affects the catalytic activity of topoisomerase IIalpha in a redox-independent manner. Furthermore, this potent inhibitory effect is not limited to a cell-free system, but is also of relevance within intact cells. DEL at micromolar concentrations was found to significantly decrease the level of topoisomerase IIalpha/DNA intermediates stabilized by the topoisomerase II poison doxorubicin in the human colon carcinoma cell line (HT29). In addition, DEL diminished the DNA-damaging properties of topoisomerase II poisons in HT29 cells without affecting the level of sites sensitive to formamidopyrimidine-DNA-glycosylase. However, the preventive effect on DNA damage exhibited an apparent maximum at a concentration of 10 microM DEL, followed by a recurrence of DNA damage at higher DEL concentrations. Furthermore, the incubation of HT29 cells with 10 microM DEL resulted in a decrease of etoposide (ETO)-induced DNA strand breaks. However, the level of ETO-stabilized covalent topoisomerase/DNA intermediates did not affect DEL, indicating an additional mechanism of action. An impact of DEL on genes involved in the repair of DNA double-strand breaks and the onset of apoptosis has to be considered. In conclusion, the natural food constituent DEL represents, depending on the concentration range, a protective factor against the DNA-damaging effects of topoisomerase II poisons in vitro. Further studies are needed to clarify whether in vivo a high DEL intake might compromise the therapeutic outcome of these anticancer agents.

Deconstructing and Reconstructing Resilience: A Dynamic Network Approach.

Resilience is still often viewed as a unitary personality construct that, as a kind of antinosological entity, protects individuals against stress-related mental problems. However, increasing evidence indicates that maintaining mental health in the face of adversity results from complex and dynamic processes of adaptation to stressors that involve the activation of several separable protective factors. Such resilience factors can reside at biological, psychological, and social levels and may include stable predispositions (such as genotype or personality traits) and malleable properties, skills, capacities, or external circumstances (such as gene-expression patterns, emotion-regulation abilities, appraisal styles, or social support). We abandon the notion of resilience as an entity here. Starting from a conceptualization of psychiatric disorders as dynamic networks of interacting symptoms that may be driven by stressors into stable maladaptive states of disease, we deconstruct the maintenance of mental health during stressor exposure into time-variant dampening influences of resilience factors onto these symptom networks. Resilience factors are separate additional network nodes that weaken symptom-symptom interconnections or symptom autoconnections, thereby preventing maladaptive system transitions. We argue that these hybrid symptom-and-resilience-factor networks provide a promising new way of unraveling the complex dynamics of mental health.

Oak ellagitannins suppress the phosphorylation of the epidermal growth factor receptor in human colon carcinoma cells.

The ellagitannins castalagin and vescalagin, and the C-glycosides grandinin and roburin E as well as ellagic acid were found to potently inhibit the growth of human colon carcinoma cells (HT29) in vitro. In a cell-free system these compounds were identified as potent inhibitors of the protein tyrosine kinase activity of the epidermal growth factor receptor (EGFR) with IC 50 values in the low nanomolar range. To address the question of whether the interference with the activity of the isolated EGFR also plays a role within intact cells, effects on the phosphorylation status of the EGFR, as a measure for its activity, were determined in HT29 cells. As exemplified for castalagin and grandinin, both the nonglycosylated and the glycosylated ellagitannins effectively suppressed EGFR phosphorylation, but only at concentrations > or =10 microM, thus, in a concentration range where growth inhibition was observed. These results indicate that the suppression of EGFR-mediated signaling might contribute to the growth inhibitory effects of these compounds present in oak-matured wines and spirits such as whiskey. In contrast, despite substantial growth inhibitory properties, ellagic acid did not significantly affect EGFR phosphorylation in HT29 cells up to 100 microM.