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Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4–82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single-nucleotide polymorphisms-based analyses of 38,127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

Article highlights Professional satellite positioning services in the vicinity of the auroral oval region are frequently degraded during night-time. The distance between the user and the closest network receiver site is an important factor for the severity of the degradations, even at distances of only a few km. The cause of the disturbances are likely ionospheric structures related to activity in the auroral oval region.

Comparative animal studies have identified a trend toward a more global structural organization as brains become larger, suggesting that brain regions grow in sync as predicted by the concerted model of brain evolution. At the same time, brain plasticity studies have identified a boost in local brain structure triggered by the environment, suggesting that brain regions grow independently, as predicted by the mosaic model. Nevertheless, it is unclear whether the environment can also trigger shifts toward a more global brain structure, that is, whether phenotypic plasticity proceeds in a concerted fashion. Here, we examined the impact of radically different rearing environments on brain organization in a teleost fish, the three‐spined stickleback (Gasterosteus aculeatus). We computed novel indices of local and global brain structure across groups reared in the two environments and entered them as predictors of differences in brain and body sizes. Changes in local brain structure predicted differences in both body and brain sizes, whereas changes in global brain structure only predicted differences in brain size. Our findings highlight the emergence of brain plasticity in a population as local and global changes that are both compatible with the concerted model. [ABSTRACT FROM AUTHOR]

Introduction: The issue of the impact of religion and spirituality on mental health is a phenomenon which has recently become increasingly more accentuated. Despite the attention given to the topic, many questions still remain as to whether and how religion and spirituality affect a person's mental wellbeing. In the text below, we have focused on examining the relationship between religion and spirituality and mental health among young adults in the Czech Republic. Research also explored the idea that forgiveness can be viewed as a component of religion or spirituality. Materials and methods: The research project was executed in close cooperation with STEM/MARK, a renowned data collection agency. The methodological framework was constructed with a dual focus: leveraging standardized questionnaires to ensure data reliability and comparability while also incorporating tailored questions that delve into the participants' socioeconomic status (SES) and background details. The study unfolded across four online sessions, a format chosen for its convenience and effectiveness in facilitating participant engagement while accommodating our respondents' diverse schedules. The total sample approached comprised of 270 young adults that expressed certain form of religiosity. Results: Forgiveness and the depth of one's personal religious or spiritual history emerged as the most influential factors. Forgiveness was significantly associated with an increase in self-blame (positively), and decrease in refocusing, planning (both negatively), and putting things into perspective (negatively) (Beta = 0.25, Beta = -0.06, and Beta = -0.16, respectively). In contrast, a deeper personal religious history was positively associated with self-blame, rumination, and refocusing (Beta = 0.22, Beta = 0.13, and Beta = 0.15, respectively). Conclusion: The finding that forgiveness may be a risk factor associated with regularly elevated depressive symptoms, stress, and maladaptive coping strategies such as self-blame and ruminating over problems, while negatively affecting physical, psychological, and environmental quality of life, clearly points to the need to examine the inner aspects of individual religions and spiritualities. These findings suggest that religious and spiritual beliefs may play a key role in how people experience and manage the emotional burdens and difficulties of life. [ABSTRACT FROM AUTHOR]

IntroductionDiffusion Weighted Imaging (DWI), which is based on Echo Planar Imaging (EPI) protocols, is becoming increasingly important for neurosurgical applications. However, its use in this context is limited in part by significant spatial distortion inherent to EPI.MethodWe evaluated an efficient algorithm for EPI distortion correction (EPIC) across 814 DWI scans from 250 brain tumor patients and quantified the magnitude of geometric distortion for whole brain and multiple brain regions.ResultsEvaluation of the algorithm's performance revealed significantly higher mutual information between T1-weighted pre-contrast images and corrected b = 0 images than the uncorrected b = 0 images (p < 0.001). The distortion magnitude across all voxels revealed a median EPI distortion effect of 2.1 mm, ranging from 1.2 mm to 5.9 mm, the 5th and 95th percentile, respectively. Regions adjacent to bone-air interfaces, such as the orbitofrontal cortex, temporal poles, and brain stem, were the regions most severely affected by DWI distortion.ConclusionUsing EPIC to estimate the degree of distortion in 814 DWI brain tumor images enabled the creation of a topographic atlas of DWI distortion across the brain. The degree of displacement of tumors boundaries in uncorrected images is severe but can be corrected for using EPIC. Our results support the use of distortion correction to ensure accurate and careful application of DWI to neurosurgical practice.

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single-nucleotide polymorphisms-based analyses of 38,127 cross-sectional MRIs showed a similar pattern of genetic volume–volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

Background: Overexpression of epidermal growth factor receptor (EGFR), and downstream pathway activation appears to be a common oncogenic driver in the majority of head and neck squamous cell cancers (HNSCCs); yet targeting EGFR for the treatment of HNSCC has met with limited success. Apart from the anti-EGFR antibody cetuximab, no small molecule EGFR/tyrosine kinase inhibitors (TKIs) have progressed to routine clinical use. The aim of this study was to determine factors contributing to the lack of response to TKIs and identify alternative therapeutic vulnerabilities. Methods: Genomic and transcriptomic sequencing, high-throughput compound screens, overexpression and siRNA knockdown, western blot, in vivo xenograft studies. Findings: We derived three pairs of isogenic gefitinib (TKI)-sensitive and resistant patient-derived HNSCC cell lines. Genomic sequencing of gefitinib-resistant cell lines identified a lack of activating and resistance-associated EGFR mutations. Instead, transcriptomic sequencing showed upregulated EMT gene signature in the gefitinib-resistant cells with a corresponding increase in their migratory phenotype. Additionally, the resistant cell displayed reduced growth rate. Surprisingly, while gefitinib-resistant cells were independent of EGFR for survival, they nonetheless displayed activation of downstream ERK and AKT signalling. High-throughput screening (HTS) of druggable, small molecule libraries revealed that the gefitinib-resistant cells were particularly sensitive to inhibitors of genes involved in cell cycle and mitosis, such as Aurora kinase inhibitors (AKIs), cyclin-dependent kinase (CDK) inhibitors, and microtubule inhibitors. Notably our results showed that in the EGFR inhibited state, Aurora kinases are essential for cell survival. Interpretation: Our study demonstrates that in the absence of activating EGFR mutations, HNSCCs may gain resistance to gefitinib through decreased cell proliferation, which makes them exceptionally vulnerable to cell-cycle inhibitors. Funding: Agency for Science, Technology, and Research (A*STAR), National Medical Research Council (NMRC), and the National Institutes of Health (NIH)/National Cancer Institute (NCI).

Background: Brain health is a multi-faceted concept used to describe brain physiology, cognitive function, mental health and well-being. Diseases of the brain account for one third of the global burden of disease and are becoming more prevalent as populations age. Diet, social interaction as well as physical and cognitive activity are lifestyle factors that can potentially influence facets of brain health. Yet, there is limited knowledge about the population's awareness of brain health and willingness to change lifestyle to maintain a healthy brain. This paper introduces the Global Brain Health Survey protocol, designed to assess people's perceptions of brain health and factors influencing brain health.Methods: The Global Brain Health Survey is an anonymous online questionnaire available in 14 languages to anyone above the age of 18 years. Questions focus on (1) willingness and motivation to maintain or improve brain health, (2) interest in learning more about individual brain health using standardized tests, and (3) interest in receiving individualized support to take care of own brain health. The survey questions were developed based on results from a qualitative interview study investigating brain health perceptions among participants in brain research studies. The survey includes 28 questions and takes 15–20 min to complete. Participants provide electronically informed consent prior to participation. The current survey wave was launched on June 4, 2019 and will close on August 31, 2020. We will provide descriptive statistics of samples distributions including analyses of differences as a function of age, gender, education, country of residence, and we will examine associations between items. The European Union funded Lifebrain project leads the survey in collaboration with national brain councils in Norway, Germany, and Belgium, Brain Foundations in the Netherlands and Sweden, the National University of Ostroh Academy and the Women's Brain Project.Discussion: Results from this survey will provide new insights in peoples' views on brain health, in particular, the extent to which the adoption of positive behaviors can be encouraged. The results will contribute to the development of policy recommendations for supporting population brain health, including measures tailored to individual needs, knowledge, motivations and life situations.

Introduction: Depressive disorder, as one of the most common mental illnesses, adversely affects the lives and health of many people around the world. It occurs at any age, but most commonly between the ages of 20 and 40. Worldwide, approximately 100 million people suffer from depressive disorders each year, with many individuals experiencing partial treatment response or treatment resistance, which continually increases the need to find effective prevention and treatment strategies, as well as to monitor and evaluate currently used approaches in routine clinical practice. Materials and methods: The more broadly conceived study, working title UMBRELLA, was a non-interventional, observational, multicentre study, the first phase of which focused on the so-called "real world evidence" of reasons for changing psychopharmacological treatment and its detailed nature in patients suffering from a depressive episode of periodic depressive disorder. The final evaluation included data from 267 patients treated in psychiatric outpatient clinics in the Czech Republic that participated in the probe into their own clinical practice. Results: Data from 74 men (27.7%) and 193 women (72.3%) with a mean age of 49 years were analysed. Changes in treatment were made by the physician based on an assessment of the residual symptoms present, with persistent depressed mood, fatigue and anhedonia being the most common problems. The most commonly used medications included antidepressants (e.g., escitalopram, venlafaxine, sertraline), atypical antipsychotics (e.g., quetiapine), and classic antipsychotics (e.g., chlorprothixene). Adjustments to pharmacological treatment were most commonly made by manipulating antidepressants, changing the active ingredient, or modifying their daily doses. Discussion and conclusion: The present naturalistic observational study mapped the reasons for the change in pharmacological approach and the actual nature of the newly chosen treatment strategy. The observed heterogeneity of pharmacological treatment manipulation patterns confirms that the treatment of depressive episodes in clinical practice follows an individualized approach for each individual patient. Here, we encounter a desire for the application of recommended practices in the treatment of this widespread mental illness, which very effectively describe the treatment of initial episodes and, in the case of recurrent episodes, should provide the basic principles of a therapeutic approach to the management of this problem. The finding that, even in the context of recurrent episodes of periodic depressive disorder, effective intervention can be achieved by increasing the dose of antidepressant medication or changing it, supports the drive to educate specialists and practitioners in these basic treatment approaches. Overall, the study provides information that reflects common clinical practice and underscores the importance of initiating a strategy to change the pharmacological approach in any patient, at any stage of the treatment of this mental illness. [ABSTRACT FROM AUTHOR]

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Introduction: Young adulthood is a transitional period between adolescence and adulthood. Due to the unique pressures of taking on a new social role and associated uncertainties, young adults are at heightened risk for drug and alcohol use. Furthermore, adverse childhood experiences (ACEs) increases the likelihood of using maladaptive coping strategies such as using substances to avoid or soothe negative emotions. The current review aimed to summarize the associations between exposure to ACEs before the age of 18 years and subsequent drug or alcohol use between the ages of 18 and 25 years. Methods: The review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search of the Web of Science, PubMed, and PsycINFO databases was conducted in February 2022. Results: The initial search yielded 7178 articles, with 777 duplicates. Consequently, 6401 titles were inspected for relevance. After reading the full text, 88 articles were included in the review. Conclusion: This review provides clear evidence that exposure to multiple ACEs is a robust risk factor for the use of alcohol, cannabis and other drugs by young adults. Poor self-regulation and maladaptive coping strategies were identified as mechanisms explaining this link; however, further detailed research is needed. [ABSTRACT FROM AUTHOR]