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BackgroundImagery Rescripting (ImRs) is a promising intervention to reduce symptoms associated with aversive memories, but little is known about its working mechanisms. The present study investigates whether ImRs increases perceived mastery and attenuates emotional reactivity to memory retrieval on a subjective and physiological level.MethodsSeventy-nine individuals reporting memories of distressing real-life events were randomly allocated to ImRs, positive imagery (PI), or no-intervention control (NIC). The memory was reactivated before the intervention and at 1-week follow-up to assess subjective measures and physiological reactivity (heart rate [HR], skin conductance level [SCL], and facial electromyography activity [EMG]) during memory retrieval.ResultsImRs was superior to PI and NIC on subjective memory distress and helplessness, but not on other emotions. ImRs did not exceed PI and NIC in reducing state stress symptoms or increasing perceived mastery. Physiological reactivity (HR, EMG) decreased from pre-intervention to follow-up with no differences between groups.ConclusionsPositive effects of ImRs on helplessness and distress were found. Null findings regarding mastery might result from timing of its assessment or the fact that rather high-functioning participants were included. The lack of between group differences on physiological responses indicates that ImRs did not exceed habituation effects in the present sample.

Preliminary evidence suggests childhood maltreatment to play a causal role in the development and maintenance of obsessive-compulsive disorder (OCD). However, both the effect of childhood maltreatment on the course of OCD treatment and the role of specific subtypes of maltreatment remain largely unknown. This study aimed to investigate the relationship between childhood maltreatment and the severity and time course of OCD symptoms within a clinical sample of OCD patients (N = 68). We hypothesized that higher levels of childhood maltreatment in OCD patients would be associated with higher symptom severity and worse treatment outcomes. Assessments of childhood maltreatment, OCD symptomatology, and related variables were completed in a sample of OCD patients before and after inpatient treatment as well as at 6 month follow-up. Emotional abuse, sexual abuse and neglect were highly prevalent in our sample. Additionally, the severity of experienced childhood maltreatment was associated with higher OCD symptom severity, with the strongest association found for emotional abuse. Hierarchical linear models indicated that patients with childhood maltreatment showed higher OCD symptom severity at pre-treatment, post-treatment, and follow-up compared to patients without these experiences. However, childhood maltreatment did not moderate symptom improvement during treatment. Thus, although childhood maltreatment is not related to treatment outcome, it is highly prevalent among OCD patients and childhood trauma survivors still show higher OCD symptom severity after treatment. Therefore, childhood maltreatment should be considered in psychological interventions in individuals with OCD.

Sleep disturbances are highly prevalent in traumatized refugees and often persist despite treatment, and adapted scalable interventions are needed. The group intervention 'Sleep Training adapted for Refugees' (STARS) is a culturally- and context-sensitive approach based on evidence-based treatments for sleep disturbances (e.g. CBT-I, IRT). This study evaluated the feasibility, acceptability, and effectiveness of STARS. A randomized-controlled trial (STARS vs. waitlist) with 47 young male Afghan refugees was conducted in a routine clinical setting (DRKS-ID: DRKS00024419) with pre-, post- and 3-month follow-up assessments. The primary outcome was insomnia severity (Insomnia Severity Index); secondary outcomes included PTSD, anxiety and depression symptoms, nightmares, coping with nightmares, fear of sleep, selected sleep diary measures, and quality of life. The data were analysed using mixed models. Adherence to STARS was high (dropout = 17.4%, average attended sessions = 77%) as was client satisfaction ( = 12.74, = 2.08). A medium to large significant effect of time was observed for insomnia severity (  = 0.96) and most secondary measures (except nightmares and fear of sleep). However, there was no significant interaction with condition at post-treatment for the primary outcome (  = 0.29) and most secondary outcomes; the only exceptions were increased coping with nightmares, decreased daytime sleep, and time in bed. STARS appears feasible for treating sleep disturbances in traumatized refugees in a routine clinical setting, showing moderate to large within-group effects. However, it was not superior to the waitlist, likely due to unexpected improvements in the waitlist group. Adjustments to STARS may enhance its efficacy. Further research is needed to determine how STARS can be a scalable add-on treatment for sleep disturbances in traumatized refugees and asylum seekers. German Clinical Trials Register identifier: DRKS00024419..

Background Although effective treatments for smoking cessation are available, long-term abstinence is the exception rather than the norm. Accordingly, there is a need for novel interventions that potentially improve clinical outcome. Although implicit information processing biases, for example approach biases for smoking-related stimuli, are ascribed a dominant role in the maintenance of tobacco dependence, these biases are hardly targeted in current treatment. Past research has shown that so-called Approach Bias Modification (AppBM) trainings, aiming to modify this bias, lead to improved long-term abstinence in abstinent alcoholic inpatients when delivered as an add-on to treatment-as-usual. Findings on the efficacy of AppBM in smoking have been inconsistent. The present large-scale clinical trial pursues two goals. First, it aims to investigate the efficacy of AppBM as an add-on to treatment-as-usual in a representative sample of adult smokers. Second, possible mechanisms of change are investigated. Methods The study is a randomized-controlled, double-blind, parallel-group superiority trial. We aim at a final sample of at least 336 adult smokers. Participants are allocated with a 1:1:1 allocation ratio to one of the following conditions: (1) treatment-as-usual + AppBM, (2) treatment-as-usual + Sham, (3) treatment-as-usual only. During the add-on training, participants are presented smoking-related and positive pictures and are instructed to respond by either pushing or pulling a joystick, depending on the tilt of the pictures (5 ○ to the left/right). During AppBM, all smoking-related pictures are tilted in the direction that is associated with pushing, thereby aiming to train an avoidance bias for smoking. All positive pictures are tilted in the direction associated with pulling. During Sham, the contingency is 50/50. Participants are assessed before and after the intervention and at a 6-month follow-up. The primary outcome is prolonged abstinence, and secondary outcomes include smoking-related variables and psychological distress. Additionally, the motivational significance of smoking-related stimuli (i.e., approach bias, valence) is assessed with different experimental tasks (Approach-Avoidance Task; Single Target Implicit Association Test) and psychophysiological measures. Discussion This is the first large-scale clinical trial investigating the efficacy of AppBM as an add-on in smokers including a TAU only condition. Additionally, it is the first study to systematically investigate potential mechanisms mediating the effects of treatment on clinical outcome. Trial registration German Clinical Trials Register, DRKS00019221 , 11/11/2019

Lower cardiac vagal control (CVC), which is often understood as an indicator for impaired regulatory processes, is assumed to predict the development of depressive symptoms. As this link has not been consistently demonstrated, sleep quality has been proposed as a moderating factor. However, previous studies were limited by non-representative samples, cross-sectional data, and focused on CVC as a physiological indicator for impaired regulatory processes, but neglected corresponding subjective measures. Therefore, we investigated whether sleep quality moderates the effects of CVC (quantified by high-frequency heart rate variability) and self-reported regulatory processes (self- and emotion-regulation) on concurrent depressive symptoms and on depressive symptoms after three months in a representative sample (N = 125). Significant interactions between CVC and sleep quality (in women only), as well as self-/emotion-regulation and sleep quality emerged, whereby higher sleep quality attenuated the relation between all risk factors and current depressive symptoms (cross-sectional data). However, there were no significant interactions between those variables in predicting depressive symptoms three months later (longitudinal data). Our cross-sectional findings extend previous findings on sleep quality as a protective factor against depressive symptoms in the presence of lower CVC and subjective indices of impaired regulatory processes. In contrast, our conflicting longitudinal results stress the need for further investigations.

Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well‐defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward‐lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin‐A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell‐instructive material parameter in the field of biomaterial‐guided tissue regeneration. The influence of 3D surface curvature on stem cell migration and differentiation is reported. Concave surfaces enable the cell body to lift off the surface resulting in increased motility while on convex surfaces, cytoskeletal tension induces nuclear deformation and enhances osteogenic differentiation. The study reveals curvature‐sensation of stem cells with relevance for biomaterial design and tissue regeneration.

Several lines of evidence implicate immune abnormalities in the pathophysiology of severe mental disorders (SMD) and comorbid mental disorders. Here, we use the data from genome-wide association studies (GWAS) of autoimmune diseases and mental phenotypes associated with SMD to disentangle genetic susceptibilities of immune abnormalities in SMD. We included 1004 patients with SMD and 947 healthy controls (HC) and measured plasma levels of IL-1Ra, sIL-2R, gp130, sTNFR-1, IL-18, APRIL, and ICAM-1. Polygenic risk scores (PRS) of six autoimmune disorders, CRP, and 10 SMD-related mental phenotypes were calculated from GWAS. General linear models were applied to assess the association of PRS with immune marker abnormalities. We found negative associations between PRS of educational attainment and IL-1Ra ( P  = 0.01) and IL-18 ( P  = 0.01). There were nominal positive associations between PRS of psoriasis and sgp130 ( P  = 0.02) and PRS of anxiety and IL-18 ( P  = 0.03), and nominal negative associations between PRS of anxiety and sIL-2R ( P  = 0.02) and PRS of educational attainment and sIL-2R ( P  = 0.03). Associations explained minor amounts of the immune marker plasma-level difference between SMD and HC. Different PRS and immune marker associations in the SMD group compared to HC were shown for PRS of extraversion and IL-1Ra ([interaction effect (IE), P  = 0.002), and nominally for PRS of openness and IL-1Ra (IE, P  = 0.02) and sTNFR-1 (IE, P  = 0.04). Our findings indicate polygenic susceptibilities to immune abnormalities in SMD involving genetic overlap with SMD-related mental phenotypes and psoriasis. Associations might suggest immune genetic factors of SMD subgroups characterized by autoimmune or specific mental features.

ObjectivePatients with cancer may display elevated levels of B-type natriuretic peptide (BNP) and high-sensitive troponin T (hsTnT) without clinical manifestation of cardiac disease. This study aimed to evaluate circulating cardiovascular hormones and hsTnT and their association with mortality in cancer.MethodsWe prospectively enrolled 555 consecutive patients with a primary diagnosis of cancer and without prior cardiotoxic anticancer therapy. N-terminal pro BNP (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), copeptin, hsTnT, proinflammatory markers interleukin 6 (IL-6) and C reactive protein (CRP), and cytokines serum amyloid A (SAA), haptoglobin and fibronectin were measured. All-cause mortality was defined as primary endpoint.ResultsDuring a median follow-up of 25 (IQR 16–31) months, 186 (34%) patients died. All cardiovascular hormones and hsTnT levels rose with tumour stage progression. All markers were significant predictors of mortality with HRs per IQR of 1.54 (95% CI 1.24 to 1.90, p<0.001) for NT-proBNP, 1.40 (95% CI 1.10 to 1.79, p<0.01) for MR-proANP, 1.31 (95% CI 1.19 to 1.44, p<0.001) for MR-proADM, 1.21 (95% CI 1.14 to 1.30, p<0.001) for CT-proET-1, 1.22 (95% CI 1.04 to 1.42, p=0.014) for copeptin and 1.21 (95% CI 1.13 to 1.32, p<0.001) for hsTnT, independent of age, gender, tumour entity and stage, and presence of cardiac comorbidities. NT-proBNP, MR-proANP, MR-proADM and hsTnT displayed a significant correlation with IL-6 and CRP.ConclusionsCirculating levels of cardiovascular peptides like NT-proBNP, MR-proANP, MR-proADM, CT-pro-ET-1 and hsTnT were elevated in an unselected population of patients with cancer prior to induction of any cardiotoxic anticancer therapy. The aforementioned markers and copeptin were strongly related to all-cause mortality, suggesting the presence of subclinical functional and morphological myocardial damage directly linked to disease progression.

ObjectiveChildren and adults with repaired tetralogy of Fallot (rTOF) have an impaired exercise capacity, a less active lifestyle and an increased long-term risk of adverse outcomes compared with healthy peers. This study aimed to summarise the current evidence for the effectiveness and safety of exercise training interventions in patients with rTOF.MethodsPubMed/MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus and reference lists of relevant articles were searched for prospective studies published by November 2021. Random-effects meta-analysis and descriptive synthesis were performed to assess the effectiveness and safety of exercise training in patients with rTOF.ResultsOf the 9677 citations identified, 12 articles were included that reported on 10 unique studies and covered 208 patients with rTOF (range of mean/median age: 7.4–43.3 years). All studies implemented 2 to 7 aerobic or respiratory training sessions per week with durations ranging from 6 to 26 weeks. Meta-analysis of the included randomised controlled trials showed that exercise training was associated with a significant improvement in peak VO2 (pooled mean difference: +3.1 mL/min/kg; 95% CI: 0.76 to 5.36 mL/min/kg, p=0.019). Cardiac imaging studies revealed no subclinical adverse remodelling after the exercise interventions. No serious adverse events including arrhythmias were reported in these studies.ConclusionCurrent evidence suggests that exercise training can improve exercise capacity in patients with rTOF with a low risk for adverse events. Exercise prescription may be a safe and effective tool to help improving outcomes in patients with rTOF.PROSPERO registration numberCRD42021292809.

Wildfire occurrence is influenced by climate, vegetation and human activities. A key challenge for understanding the risk of fires is quantifying the mediating effect of vegetation on fire regimes. Here, we explore the relative importance of Holocene land cover, land use, dominant functional forest type, and climate dynamics on biomass burning in temperate and boreo-nemoral regions of central and eastern Europe over the past 12 kyr. We used an extensive data set of Holocene pollen and sedimentary charcoal records, in combination with climate simulations and statistical modelling. Biomass burning was highest during the early Holocene and lowest during the mid-Holocene in all three ecoregions (Atlantic, continental and boreo-nemoral) but was more spatially variable over the past 3-4 kyr. Although climate explained a significant variance in biomass burning during the early Holocene, tree cover was consistently the highest predictor of past biomass burning over the past 8 kyr. In temperate forests, biomass burning was high at ∼ 45% tree cover and decreased to a minimum at between 60% and 70% tree cover. In needleleaf-dominated forests, biomass burning was highest at ∼60 %-65%tree cover and steeply declined at > 65% tree cover. Biomass burning also increased when arable lands and grasslands reached ∼15 %-20 %, although this relationship was variable depending on land use practice via ignition sources, fuel type and quantities. Higher tree cover reduced the amount of solar radiation reaching the forest floor and could provide moister, more wind-protected microclimates underneath canopies, thereby decreasing fuel flammability. Tree cover at which biomass burning increased appears to be driven by warmer and drier summer conditions during the early Holocene and by increasing human influence on land cover during the late Holocene. We suggest that longterm fire hazard may be effectively reduced through land cover management, given that land cover has controlled fire regimes under the dynamic climates of the Holocene.