Genome-wide Nucleotide-Resolution Mapping of DNA Replication Patterns, Single-Strand Breaks, and Lesions by GLOE-Seq.

DNA single-strand breaks (SSBs) are among the most common lesions in the genome, arising spontaneously and as intermediates of many DNA transactions. Nevertheless, in contrast to double-strand breaks (DSBs), their distribution in the genome has hardly been addressed in a meaningful way. We now present a technique based on genome-wide ligation of 3'-OH ends followed by sequencing (GLOE-Seq) and an associated computational pipeline designed for capturing SSBs but versatile enough to be applied to any lesion convertible into a free 3'-OH terminus. We demonstrate its applicability to mapping of Okazaki fragments without prior size selection and provide insight into the relative contributions of DNA ligase 1 and ligase 3 to Okazaki fragment maturation in human cells. In addition, our analysis reveals biases and asymmetries in the distribution of spontaneous SSBs in yeast and human chromatin, distinct from the patterns of DSBs.

Neural correlates of context-dependent extinction recall in social anxiety disorder: relevance of intrusions in response to aversive social experiences.

BACKGROUND: There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event. METHODS: During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses. RESULTS: Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions. CONCLUSIONS: Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.

Decontextualized fear memories? Stronger conditioned fear responses during extinction learning and extinction recall in a safe context predict the development of long-term analog intrusions.

BACKGROUND: Difficulties in the context-dependent modulation of conditioned fear are known for posttraumatic stress disorder and may explain the occurrence of intrusive memories in safe contexts. The current study therefore investigated if reduced context-dependent modulation of conditioned fear and its underlying neural circuitry constitute risk factors for the development of analog intrusions in response to an experimental trauma. METHODS: Eighty-five healthy women participated in the trauma film paradigm to investigate the development of analog intrusions as well as explicit memory for an experimental trauma after one week and three months, respectively. Before, participants underwent a context-dependent fear conditioning paradigm during functional magnetic resonance imaging with fear acquisition in context A and extinction training in context B on a first day, as well as extinction recall in context B and fear renewal in a novel context C one day later. Skin conductance responses (SCRs) and blood oxygen level dependent responses were main outcome measures. RESULTS: In addition to stronger fear acquisition in context A, stronger conditioned fear responses in the safe context B, as indicated by stronger conditioned SCRs or stronger activation of fear expressing regions during extinction learning and recall, predicted the development of long-term analog intrusions. CONCLUSIONS: Stronger fear responses in safe and danger contexts were risk factors for the development of long-term analog intrusions and point to decontextualized fear memories and difficulties in the context-dependent modulation of conditioned fear. Altered fear conditioning processes and reduced storage of contextual information may cause the occurrence of fear independent of context.

Weathering the storm of emotions: immediate and lasting effects of reinterpretation and distancing on event-related potentials and their association with habitual use of cognitive reappraisal.

Reinterpretation and distancing, two cognitive reappraisal tactics, are known to effectively reduce negative feelings and event-related potentials (ERPs), such as the P300 and the late positive potential (LPP), in the short-term. Less is known about differential and lasting effects on ERPs as well as their association with habitual reappraisal. Fifty-seven participants were instructed to passively view or reappraise (reinterpretation, distancing) pictures that were repeatedly presented with the same instruction (active regulation phase). Thirty minutes later, these pictures were shown again without instruction for the assessment of lasting effects (re-exposure phase). ERPs were recorded and participants rated the intensity of negative feelings following picture presentation. Reappraisal led to an attenuation of the LPP, and both tactics decreased negative feelings during active regulation, whereby reinterpretation had a stronger impact on the subjective level. Passive re-exposure resulted in reduced negative feelings for previously reappraised pictures but had no lasting effects on ERPs. Higher habitual reappraisal was associated with higher P300 and early LPP amplitudes for emotional reactivity during the active regulation phase. During the re-exposure phase, higher habitual reappraisal was not related to ERPs. The current findings emphasize the effectiveness of both tactics in the short-term and lasting effects on the subjective experience of negative feelings. Enhanced emotional reactivity on the electrocortical level in individuals with a more frequent habitual use of reappraisal might indicate a higher preparedness to regulate.

[Validation of the German version of the Fear-Avoidance Beliefs Questionnaire (FABQ-D) for shoulder disorders]. / Validierung der deutschen Version des Fear-Avoidance Beliefs Questionnaire (FABQ-D) für Patient*innen mit Schulterbeschwerden.

BACKGROUND: With a prevalence of up to 30%, shoulder disorders form the third largest group of musculoskeletal complaints worldwide. Their formation and development are influenced by psychosocial factors such as movement-related fear. One of the internationally most common measurements for quantifying fear of movement is the Fear-Avoidance Beliefs Questionnaire (FABQ). OBJECTIVES: To investigate the reliability (internal consistency) and validity (structural validity, construct validity, predictive validity) of the FABQ­D in a shoulder pain population. MATERIALS AND METHODS: Subjects with shoulder pain were included in a multicenter cross-sectional study. In addition to fear-avoidance beliefs, pain intensity, subjective impairment in daily life and kinesiophobia were recorded. To this end, the FABQ­D, numeric rating scale (NRS), Shoulder and Pain Disability Index (SPADI) and the Tampa Scale for Kinesiophobia (TSK-GV) were used. RESULTS: A total of 49 subjects (24 women and 25 men) with a mean age of 41.8 years (SD = 12.8) were included. The descriptive evaluation at item level showed good internal consistency of the FABQ­D (Cronbach's α = 0.88). The homogeneity factor differs significantly between the subscales (Loevinger's H = 0.66-0.9). The correlation analyses did not show any clear convergence of the FABQ­D with the TSK-GV (r = 0.3501; p = 0.0137). A divergence to the constructs of the NRS (r = 0.1818; p = 0.2112) and SPADI (r = 0.4415; p = 0.0015) were confirmed. The hypothesis testing resulted in 42.87% of the assumed hypotheses and therefore a low construct validity. The FABQ­D and the TSK-GV showed a significant influence on the duration of the complaints (R2 = 0.3652; p ≤ 0.0001). It was also shown that the greatest factors for a high FABQ­D value were functional impairment (SPADI) and duration of symptoms (R2 = 0.3066; p = 0.0002). The subgroup analysis showed a significantly higher FABQ­D value in older subjects (40-65 years; t = 3.8084/df = 47, p = 0.0002). CONCLUSION: The FABQ­D is a reliable measurement tool. The construct validity should be further investigated in future studies. This study reproduced results from previous studies in other populations. The FABQ­D appears to be an adequate measurement tool for quantifying fear of movement in patients with shoulder disorders.

[Innovative interventions in pain physiotherapy : Advancing care for people with chronic pain]. / Innovative Maßnahmen in der Schmerzphysiotherapie : Impulse für eine bessere Versorgung von Menschen mit chronischen Schmerzen.

BACKGROUND: Chronic pain, with a prevalence of at least 17%, is a costly health problem associated with a high burden of disease. Musculoskeletal chronic pain is particulary common, which in many cases is treated with physiotherapy. AIM: The aim of this paper is to provide an overview of innovative, promising physiotherapy interventions in pain management, to present their effectiveness and to discuss their implementation in healthcare. METHODS: A narrative review was conducted. The Cochrane, Medline (via PubMed) and PEDro databases were searched using the search terms chronic pain, physiotherapy, prevention, pain education, behavioural intervention, eHealth, and systematic review as well as chronic pain, guideline and relevant synonyms. RESULTS: One guideline review, two guidelines and ten systematic reviews were included. Chronic pain prevention, digital health apps, lifestyle interventions and behavioural approaches were identified as promising and effective interventions for people with chronic pain, showing the potential to meaningfully complement pain physiotherapy and improve quality of care. CONCLUSIONS: Despite the predominantly positive results from systematic reviews, implementation in everyday care is difficult due to conditions of care and the contemporary education system for physiotherapists in Germany. Health services research can play an important role in accelerating the transfer of innovations into practice.

[Patient education for acute low back pain : Contents of pain education in patients with acute non-specific low back pain - a scoping review]. / Edukation bei akuten lumbalen Rückenschmerzen : Inhalte der Schmerzedukation bei Patient*innen mit akuten unspezifischen lumbalen Rückenschmerzen ­ ein Scoping-Review.

OBJECTIVE: The objective of the review is to map the content of intervention education in people with acute nonspecific lumbar low back pain (LBP) to make it available in a synopsis. BACKGROUND: In the care of people with acute non-specific LBP, education is recommended as an elementary treatment component. However, the proposed content is proving to be heterogenic and the question arises as to how education should be designed in the future. METHOD: A systematic literature search and content analysis of studies with content on pain education was conducted as part of a scoping review. Inclusion criteria were: provision of relevant information on the content of pain education, patients with acute nonspecific low back pain, 18 years or older, publication in English or German. The search was conducted in the Medline, CINAHL, Cochrane Library, and PEDro databases and supplemented by a hand search. The search was completed in February 2021. RESULTS: A total of 4239 hits were identified, of which 90 studies were included. A wide range of content was found and clustered into ten categories. The most frequent statements were in the categories "recommendations for dealing with LRS," "education, reassuring aspects, and relieving basic messages," and "information and recommendations about medications." CONCLUSION: The teaching of pathoanatomical information can potentially trigger or increase anxiety and worry, whereas information on neurophysiological mechanisms of pain development and processing is more likely to have an anxiety-reducing effect. The results can contribute to the design of the intervention in different settings.

[Kinesiophobia in shoulder disorders : Validation of the German version of the Tampa scale for kinesiophobia (TSK-GV)]. / Kinesiophobie bei Schulterbeschwerden : Validierung der deutschen Version der Tampa Scale for Kinesiophobia (TSK-GV).

BACKGROUND: With a prevalence of 7-30%, shoulder disorders form the third largest group of musculoskeletal complaints. Their formation and development is influenced by, e.g. psychological factors. The Tampa scale for kinesiophobia (TSK) is the most common measure for quantifying fear of movement. OBJECTIVES: To investigate the reliability and validity of the German version of the TSK (TSK-GV) in a shoulder pain population. MATERIALS AND METHODS: Subjects with shoulder pain were included in a multicenter cross-sectional study. In addition to kinesiophobia, pain intensity, subjective impairment in daily life and fear-avoidance beliefs were recorded. RESULTS: A total of 49 subjects (24 women and 25 men) with a mean age of 41.8 (SD = 12.8) were included. The descriptive evaluation at item level showed good internal consistency (Cronbach's α = 0.81). The homogeneity of the scale is poor (Loevinger's H = 0.35). The correlations did not show any clear convergence of the TSK-GV with the fear-avoidance beliefs questionnaire (FABQ) (r = 0.3501; p = 0.0137). The divergent validity was confirmed for both the numerical rating scale (NRS) (r = 0.1216; p = 0.4052) and the shoulder pain and disability index (SPADI) (r = 0.2571; p = 0.0745). The hypothesis testing resulted in 28.57% accepted hypotheses. There was a significant influence of the TSK-GV and the FABQ on the duration of complaints (R2 = 0.3652; p ≤ 0.0001), as well as an explained variance of the duration of complaints on the TSK-GV of R2 = 0.1834 (p = 0.0021). The subgroup analysis showed a significantly higher degree of kinesiophobia in male subjects (t = 3.8084/df = 47; p = 0.0002). CONCLUSION: The TSK-GV is a reliable measurement tool. The construct validity should be further investigated in future studies. This study shows comparable values to previous studies in other populations. The TSK-GV is to date the only validated German language measure for recording fear of movement in shoulder disorders and shows an acceptable fit for this population.

Validation and investigation of cross cultural equivalence of the Fremantle back awareness questionnaire - German version (FreBAQ-G).

BACKGROUND: Disrupted self-perception of the low back might contribute to chronic non-specific low back pain. The Fremantle back awareness questionnaire is a simple questionnaire to assess back specific self-perception. The questionnaire has recently been translated to German (FreBAQ-G). The aim was to further investigate the psychometric properties of the FreBAQ-G, to evaluate its cross cultural validity in patients with chronic non-specific LBP and to explore potential relationships between body perception, pain, disability and back pain beliefs. METHODS: In this cross-sectional multicentre study, sample data were merged with data from the validation sample of the original English version to examine cross-cultural validity. Item Response Theory was used to explore psychometric properties and differential item function (DIF) to evaluate cross-cultural validity and item invariance. Correlations and multiple linear regression analyses were used to explore the relationship between altered back specific self- perception and back pain parameters. RESULTS: Two hundred seventy-two people with chronic low back pain completed the questionnaires. The FreBAQ-G showed good internal consistency (Cronbach's alpha = 0.84), good overall reliability (r = 0.84) and weak to moderate scalability (Loevinger Hj between 0.34 and 0.48). The questionnaire showed unidimensional properties with factor loadings between 0.57 and 0.80 and at least moderate correlations (r > 0.35) with pain intensity, pain related disability and fear avoidance beliefs (FABQ total - and subscores). Item and test properties of the FreBAQ-G are given. Only item 7 showed uniform DIF indicating acceptable cross-cultural validity. CONCLUSIONS: Our results indicate that the FreBAQ-G is a suitable questionnaire to measure back specific self-perception, and has comparable properties to the English-language version.

Cross-cultural adaptation and validation of the German Central Sensitization Inventory (CSI-GE).

BACKGROUND: The Central Sensitization Inventory (CSI) is a screening tool designed to detect symptoms related to Central Sensitization (CS) and Central Sensitivity Syndromes (CSS) by measuring the degree of related phenomena. The objective of this study was to create a German, culturally-adapted version of the CSI and to test its psychometric properties. METHODS: A German version of the CSI (CSI-GE) was developed, culturally-adapted, and pretested for comprehensibility. The psychometric properties of the resulting version were validated in a clinical study with chronic pain and pain-free control subjects. To assess retest reliability, the CSI-GE was administered twice to a subgroup of patients. Structural validity was tested using factor analyses. To investigate construct validity a hypotheses testing approach was used, including (1) correlations between the CSI-GE and several other well-established questionnaires as well as (2) an investigation of the CSI-GE discriminative power between different subgroups of participants believed to have different degrees of CS. RESULTS: The CSI-GE showed excellent reliability, including high test-retest characteristics. Factor analyses confirmed a bi-factor dimensionality as has been determined previously. Analysing construct validity 6 out of 11 hypotheses (55%) were met. CSI-GE scores differentiated between subgroups according to expectations. Correlations between CSI-GE scores and other questionnaires suggested that none of the correlated constructs was identical, but there was overlap with other questionnaires based on symptom load. Several correlations did not fit with our current understanding of CS. CONCLUSION: The CSI-GE appears to be a reliable tool for measuring CS/CSS-related symptomatology. Whether this implies that the CSI-GE measures the degree of CS within an individual subject remains unknown. The resulting score should be interpreted cautiously until further clarification of the construct.

[On the move-Prevention of chronic pain with physical activity and movement]. / "On the Move" ­ Prävention chronischer Schmerzen durch körperliche Aktivität und Bewegung.

BACKGROUND: Sufficient physical activity and exercise shows a variety of health-promoting positive effects. In the context of pain therapy, promotion of physical activity could be an important contribution to primary, secondary and tertiary prevention of chronic pain. OBJECTIVES: The aim is to investigate the relationship between physical activity and chronic pain, the preventive effect of physical activity on pain and the factors to successfully promote physical activity in people with chronic pain. METHODS: For this narrative review databases of the Cochrane Library, MEDLINE (via PubMed) and the Physiotherapy Evidence Database (PEDro) were searched for reviews and studies with the keywords chronic pain, physical activity, movement, exercise and prevention. RESULTS: A total of 10 reviews, 10 clinical studies and 4 surveys were included and summarized. CONCLUSION: Although the evidence base on this topic is still insufficient, positive effects of physical activity on the prevention of chronic pain could be demonstrated. Interventions for people with chronic pain that sustainably increase physical activity should take into account individual resources, address barriers such as maladaptive beliefs, and create positive movement experiences.

Correction to: Concurrent validity and reliability of measuring range of motion during the cervical flexion rotation test with a novel digital goniometer.

An amendment to this paper has been published and can be accessed via the original article.

Concurrent validity and reliability of measuring range of motion during the cervical flexion rotation test with a novel digital goniometer.

BACKGROUND: Headache is a common and costly health problem. Although the pathogenesis of headache is heterogeneous, reported contributing factors are dysfunctions of the upper cervical spine. The flexion rotation test (FRT) is a commonly used diagnostic test to detect upper cervical movement impairment. A digital goniometer may support precise measurement of movement impairment in the upper cervical spine. However, its reliability and validity is not assessed, yet. The aim of this study was to investigate the reliability and validity of the digital goniometer compared to an ultrasound-based movement analysis system. METHODS: Two separate cross-sectional studies were conducted using the digital goniometer EasyAngle (Meloq AB, Stockholm, Sweden) for a) investigating the concurrent validity of upper cervical range of motion (ROM) during the FRT and b) determining the inter- and intra-rater reliability in the target population of patients with head and neck pain. Sixty-two participants, 39 with and 23 without head and neck pain, were recruited for the concurrent validity study. For the reliability study, a total of 50 participants were recruited. Intraclass correlation coefficients (ICC) and Bland Altmann plots were used to assess validity and ICC values, Bland Altmann plots as well as Kappa coefficients were used for estimating intra-rater and inter-rater reliability. RESULTS: Concurrent validity was strong with an ICC (2,1) of 0.97 for ROM to either side (95%CI = 0.95-0.98). Bland Altman Plots revealed a mean difference between measurement systems of 0.5° for the left and 0.11° for the right side. The inter-rater ICC (2,1) was 0.66 (95%CI 0.47-0.79, p <  0.001, SEM 6.6°), indicating good reliability. The limits of agreement were between 10.25° and - 11.89°, the mean difference between both raters was - 0.82°. Intra-rater reliability for the measurement of ROM during the FRT was between 0.96 (ICC 3,1) for rater 1 and 0.94 (ICC 3,1) for rater 2. CONCLUSIONS: The digital goniometer demonstrated strong concurrent validity and good to strong reliability and can be used in clinical practice to accurately determine movement impairment in the upper cervical spine. TRIAL REGISTRATION: German Registry of Clinical Trials DRKS00013051 .

Dynamic brain network reconfiguration as a potential schizophrenia genetic risk mechanism modulated by NMDA receptor function.

Schizophrenia is increasingly recognized as a disorder of distributed neural dynamics, but the molecular and genetic contributions are poorly understood. Recent work highlights a role for altered N-methyl-d-aspartate (NMDA) receptor signaling and related impairments in the excitation-inhibitory balance and synchrony of large-scale neural networks. Here, we combined a pharmacological intervention with novel techniques from dynamic network neuroscience applied to functional magnetic resonance imaging (fMRI) to identify alterations in the dynamic reconfiguration of brain networks related to schizophrenia genetic risk and NMDA receptor hypofunction. We quantified "network flexibility," a measure of the dynamic reconfiguration of the community structure of time-variant brain networks during working memory performance. Comparing 28 patients with schizophrenia, 37 unaffected first-degree relatives, and 139 healthy controls, we detected significant differences in network flexibility [F(2,196) = 6.541, P = 0.002] in a pattern consistent with the assumed genetic risk load of the groups (highest for patients, intermediate for relatives, and lowest for controls). In an observer-blinded, placebo-controlled, randomized, cross-over pharmacological challenge study in 37 healthy controls, we further detected a significant increase in network flexibility as a result of NMDA receptor antagonism with 120 mg dextromethorphan [F(1,34) = 5.291, P = 0.028]. Our results identify a potential dynamic network intermediate phenotype related to the genetic liability for schizophrenia that manifests as altered reconfiguration of brain networks during working memory. The phenotype appears to be influenced by NMDA receptor antagonism, consistent with a critical role for glutamate in the temporal coordination of neural networks and the pathophysiology of schizophrenia.

The SyBil-AA real-time fMRI neurofeedback study: protocol of a single-blind randomized controlled trial in alcohol use disorder.

BACKGROUND: Alcohol Use Disorder is a highly prevalent mental disorder which puts a severe burden on individuals, families, and society. The treatment of Alcohol Use Disorder is challenging and novel and innovative treatment approaches are needed to expand treatment options. A promising neuroscience-based intervention method that allows targeting cortical as well as subcortical brain processes is real-time functional magnetic resonance imaging neurofeedback. However, the efficacy of this technique as an add-on treatment of Alcohol Use Disorder in a clinical setting is hitherto unclear and will be assessed in the Systems Biology of Alcohol Addiction (SyBil-AA) neurofeedback study. METHODS: N = 100 patients with Alcohol Use Disorder will be randomized to 5 parallel groups in a single-blind fashion and receive real-time functional magnetic resonance imaging neurofeedback while they are presented pictures of alcoholic beverages. The groups will either downregulate the ventral striatum, upregulate the right inferior frontal gyrus, negatively modulate the connectivity between these regions, upregulate, or downregulate the auditory cortex as a control region. After receiving 3 sessions of neurofeedback training within a maximum of 2 weeks, participants will be followed up monthly for a period of 3 months and relapse rates will be assessed as the primary outcome measure. DISCUSSION: The results of this study will provide insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback training in the treatment of Alcohol Use Disorder as well as in the involved brain systems. This might help to identify predictors of successful neurofeedback treatment which could potentially be useful in developing personalized treatment approaches. TRIAL REGISTRATION: The study was retrospectively registered in the German Clinical Trials Register (trial identifier: DRKS00010253 ; WHO Universal Trial Number (UTN): U1111-1181-4218) on May 10th, 2016.

Dynamic reconfiguration of frontal brain networks during executive cognition in humans.

The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of "dynamic network neuroscience" to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the "n-back" task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes "network flexibility," employs transient and heterogeneous connectivity between frontal systems, which we refer to as "integration." Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia.

Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

The Efficacy of Electronic Health-Supported Home Exercise Interventions for Patients With Osteoarthritis of the Knee: Systematic Review.

BACKGROUND: Osteoarthritis of the knee is the most common cause for disability and limited mobility in the elderly, with considerable individual suffering and high direct and indirect disease-related costs. Nonsurgical interventions such as exercise, enhanced physical activity, and self-management have shown beneficial effects for pain reduction, physical function, and quality of life (QoL), but access to these treatments may be limited. Therefore, home therapy is strongly recommended. However, adherence to these programs is low. Patients report lack of motivation, feedback, and personal interaction as the main barriers to home therapy adherence. To overcome these barriers, electronic health (eHealth) is seen as a promising opportunity. Although beneficial effects have been shown in the literature for other chronic diseases such as chronic pain, cardiovascular disease, and diabetes, a systematic literature review on the efficacy of eHealth interventions for patients with osteoarthritis of knee is missing so far. OBJECTIVE: The aim of this study was to compare the efficacy of eHealth-supported home exercise interventions with no or other interventions regarding pain, physical function, and health-related QoL in patients with osteoarthritis of the knee. METHODS: MEDLINE, CENTRAL, CINAHL, and PEDro were systematically searched using the keywords osteoarthritis knee, eHealth, and exercise. An inverse variance random-effects meta-analysis was carried out pooling standardized mean differences (SMDs) of individual studies. The Cochrane tool was used to assess risk of bias in individual studies, and the quality of evidence across studies was evaluated following the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: The literature search yielded a total of 648 results. After screening of titles, abstracts, and full-texts, seven randomized controlled trials were included. Pooling the data of individual studies demonstrated beneficial short-term (pain SMD=−0.31, 95% CI −0.58 to −0.04, low quality; QoL SMD=0.24, 95% CI 0.05-0.43, moderate quality) and long-term effects (pain −0.30, 95% CI −0.07 to −0.53, moderate quality; physical function 0.41, 95% CI 0.17-0.64, high quality; and QoL SMD=0.27, 95% CI 0.06-0.47, high quality). CONCLUSIONS: eHealth-supported exercise interventions resulted in less pain, improved physical function, and health-related QoL compared with no or other interventions; however, these improvements were small (SMD<0.5) and may not make a meaningful difference for individual patients. Low adherence is seen as one limiting factor of eHealth interventions. Future research should focus on participatory development of eHealth technology integrating evidence-based principles of exercise science and ways of increasing patient motivation and adherence.

Differential responses of the dorsomedial prefrontal cortex and right posterior superior temporal sulcus to spontaneous mentalizing.

Previous research suggests a role of the dorsomedial prefrontal cortex (dmPFC) in metacognitive representation of social information, while the right posterior superior temporal sulcus (pSTS) has been linked to social perception. This study targeted these functional roles in the context of spontaneous mentalizing. An animated shapes task was presented to 46 subjects during functional magnetic resonance imaging. Stimuli consisted of video clips depicting animated shapes whose movement patterns prompt spontaneous mentalizing or simple intention attribution. Based on their differential response during spontaneous mentalizing, both regions were characterized with respect to their task-dependent connectivity profiles and their associations with autistic traits. Functional network analyses revealed highly localized coupling of the right pSTS with visual areas in the lateral occipital cortex, while the dmPFC showed extensive coupling with instances of large-scale control networks and temporal areas including the right pSTS. Autistic traits were related to mentalizing-specific activation of the dmPFC and to the strength of connectivity between the dmPFC and posterior temporal regions. These results are in good agreement with the hypothesized roles of the dmPFC and right pSTS for metacognitive representation and perception-based processing of social information, respectively, and further inform their implication in social behavior linked to autism. Hum Brain Mapp 38:3791-3803, 2017. © 2017 Wiley Periodicals, Inc.

Identification of gene ontologies linked to prefrontal-hippocampal functional coupling in the human brain.

Functional interactions between the dorsolateral prefrontal cortex and hippocampus during working memory have been studied extensively as an intermediate phenotype for schizophrenia. Coupling abnormalities have been found in patients, their unaffected siblings, and carriers of common genetic variants associated with schizophrenia, but the global genetic architecture of this imaging phenotype is unclear. To achieve genome-wide hypothesis-free identification of genes and pathways associated with prefrontal-hippocampal interactions, we combined gene set enrichment analysis with whole-genome genotyping and functional magnetic resonance imaging data from 269 healthy German volunteers. We found significant enrichment of the synapse organization and biogenesis gene set. This gene set included known schizophrenia risk genes, such as neural cell adhesion molecule (NRCAM) and calcium channel, voltage-dependent, beta 2 subunit (CACNB2), as well as genes with well-defined roles in neurodevelopmental and plasticity processes that are dysfunctional in schizophrenia and have mechanistic links to prefrontal-hippocampal functional interactions. Our results demonstrate a readily generalizable approach that can be used to identify the neurogenetic basis of systems-level phenotypes. Moreover, our findings identify gene sets in which genetic variation may contribute to disease risk through altered prefrontal-hippocampal functional interactions and suggest a link to both ongoing and developmental synaptic plasticity.