Regional policy and greenfield investments in German districts

The politics and administration of institutional chang

Functional DNA methylation signatures for autism spectrum disorder genomic risk loci: 16p11.2 deletions and CHD8 variants

Background: Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (\u3e 200 ASD-risk genes), no single gene variant accounts for \u3e 1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. Gene-specific DNAm profiles have been shown to assist in the interpretation of variants of unknown significance. Therefore, we investigated the epigenome in patients with ASD or two of the most common genomic variants conferring increased risk for ASD. Genome-wide DNA methylation (DNAm) was assessed using the Illumina Infinium HumanMethylation450 and MethylationEPIC arrays in blood from individuals with ASD of heterogeneous, undefined etiology (n = 52), and individuals with 16p11.2 deletions (16p11.2del, n = 9) or pathogenic variants in the chromatin modifier CHD8 (CHD8 +/-, n = 7). Results: DNAm patterns did not clearly distinguish heterogeneous ASD cases from controls. However, the homogeneous genetically-defined 16p11.2del and CHD8 +/- subgroups each exhibited unique DNAm signatures that distinguished 16p11.2del or CHD8 +/- individuals from each other and from heterogeneous ASD and control groups with high sensitivity and specificity. These signatures also classified additional 16p11.2del (n = 9) and CHD8 (n = 13) variants as pathogenic or benign. Our findings that DNAm alterations in each signature target unique genes in relevant biological pathways including neural development support their functional relevance. Furthermore, genes identified in our CHD8 +/- DNAm signature in blood overlapped differentially expressed genes in CHD8 +/- human-induced pluripotent cell-derived neurons and cerebral organoids from independent studies. Conclusions: DNAm signatures can provide clinical utility complementary to next-generation sequencing in the interpretation of variants of unknown significance. Our study constitutes a novel approach for ASD risk-associated molecular classification that elucidates the vital cross-talk between genetics and epigenetics in the etiology of ASD

Flow on the Internet: a longitudinal study of Internet addiction symptoms during adolescence

Internet Addiction (IA) constitutes an excessive Internet use behavior with a significant impact on the user’s well-being. Online flow describes the users’ level of being absorbed by their online activity. The present study investigated age-related, gender, and flow effects on IA in adolescence. The sample comprised 648 adolescents who were assessed twice at age 16 and 18 years. IA was assessed using the Internet Addiction Test and online flow was assessed using the Online Flow Questionnaire. A three-level hierarchical model estimated age-related, gender, and online flow effects on IA symptoms and controlled for clustered random effects. IA symptoms decreased over time (for both genders) with a slower rate in males. Online flow was associated with IA symptoms and this remained consistent over time. Findings expand upon the available literature suggesting that IA symptoms could function as a development-related manifestation at the age of 16 years, while IA-related gender differences gradually increase between 16 and 18 years. Finally, the association between online flow and IA symptoms remained stable independent of age-related effects. The study highlights individual differences and provides directions for more targeted prevention and intervention initiatives for IA

MMORPG gaming and hostility predict internet addiction symptoms in adolescents: an empirical multilevel longitudinal study

Internet addiction (IA) has become an increasingly researched topic. In the present study, IA symptoms in adolescents were investigated longitudinally with specific focus on the individual’s hostility, gaming use (of Massively Multiplayer Online Role Playing Games [MMORPGs]) and gaming on the classroom level (calculated using the percentage of MMORPG players within classes). The sample comprised 648 Greek adolescents who were assessed over a two-year period (aged 16-18 years). IA symptoms were assessed with the Internet Addiction Test (IAT), and hostility with the relevant subscale of the Symptom Checklist-90 (SCL-90). A three-level hierarchical linear model was used to differentiate individual and classroom-level influences on IA symptoms at age 16 years and over time. MMORPG gamers and more hostile adolescents presented more symptoms of IA. However, being a member of a classroom with a higher percentage of MMORPG gamers appeared to be a protective factor for IA. These longitudinal data emphasize the importance of contextual factors at the level of the classroom in determining differences in IA symptoms during adolescence

Smartphone pedometers in adults with asthma: a practical approach to physical activity assessment? A pilot validation study

OBJECTIVE: The aim of this pilot validation study was to determine the accuracy of a smartphone (iPhone®) pedometer in adults with and without asthma. METHODS: : Ten adults with asthma and ten healthy controls underwent clinical assessment prior to completing two separate trials. Phase 1. standardized treadmill and self-paced walking tests. Total steps were recorded via: (i) Yamax Digiwalker™ SW800 pedometer positioned on the waistband, (ii) iPhone® pedometer positioned on the upper body, (iii) iPhone® pedometer positioned on the lower body and evaluated against a video-verified manual step-count. Phase 2. step-count was evaluated over seven-days during habitual free-living conditions via Yamax Digiwalker™ SW800 and iPhone® pedometers. RESULTS: : During treadmill walking, the iPhone® positioned on the lower body correlated strongly (r = 0.96) and produced the highest level of agreement (mean bias: -11 steps, LOA: -43 to 21 steps) in comparison to video-verified manual step-count. During self-paced walking, all devices provided an excellent step-count estimate. During free-living conditions, no difference was observed between the Yamax Digiwalker™ SW800 pedometer and iPhone® (P = 0.10) and a strong correlation (r = 0.94) and acceptable agreement (mean bias: -343, LOA: -1963 to 1276 steps) was observed. CONCLUSION: : Our findings indicate that an in-built iPhone® pedometer offers a practical approach to physical activity assessment in adults with and without asthma. Future research is now required to further validate the precision of this approach and evaluate the efficacy and effectiveness of smartphone pedometers to monitor and promote physical activity when employed during medical consultation and/or clinical research trials

The Role of Mitophagy in Glaucomatous Neurodegeneration

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential

Physical activity promotion interventions in chronic airways disease: a systematic review and meta-analysis.

Physical inactivity is common in people with chronic airways disease (pwCAD) and associated with worse clinical outcomes and impaired quality of life. We conducted a systematic review and meta-analysis to characterise and evaluate the effectiveness of interventions promoting step-based physical activity (PA) in pwCAD. We searched for studies that included a form of PA promotion and step-count outcome measure. A random-effects model was used to determine the overall effect size using post-intervention values. 38 studies (n=32 COPD; n=5 asthma; n=1 bronchiectasis; study population: n=3777) were included. Overall, implementing a form of PA promotion resulted in a significant increase in step-count: median (IQR) 705 (183-1210) when compared with usual standard care: -64 (-597-229), standardised mean difference (SMD) 0.24 (95% CI: 0.12-0.36), p<0.01. To explore the impact of specific interventions, studies were stratified into subgroups: PA promotion+wearable activity monitor-based interventions (n=17) (SMD 0.37, p<0.01); PA promotion+step-count as an outcome measure (n=9) (SMD 0.18, p=0.09); technology-based interventions (n=12) (SMD 0.16, p=0.01). Interventions promoting PA, particularly those that incorporate wearable activity monitors, result in a significant and clinically meaningful improvement in daily step-count in pwCAD

Physical activity promotion interventions in chronic airways disease: a systematic review and meta-analysis

Physical inactivity is common in people with chronic airways disease (pwCAD) and associated with worse clinical outcomes and impaired quality of life. We conducted a systematic review and meta-analysis to characterise and evaluate the effectiveness of interventions promoting step-based physical activity (PA) in pwCAD. We searched for studies that included a form of PA promotion and step-count outcome measure. A random-effects model was used to determine the overall effect size using post-intervention values. 38 studies (n=32 COPD; n=5 asthma; n=1 bronchiectasis; study population: n=3777) were included. Overall, implementing a form of PA promotion resulted in a significant increase in step-count: median (IQR) 705 (183–1210) when compared with usual standard care: −64 (−597–229), standardised mean difference (SMD) 0.24 (95% CI: 0.12–0.36), p<0.01. To explore the impact of specific interventions, studies were stratified into subgroups: PA promotion+wearable activity monitor-based interventions (n=17) (SMD 0.37, p<0.01); PA promotion+step-count as an outcome measure (n=9) (SMD 0.18, p=0.09); technology-based interventions (n=12) (SMD 0.16, p=0.01). Interventions promoting PA, particularly those that incorporate wearable activity monitors, result in a significant and clinically meaningful improvement in daily step-count in pwCAD