Abstract
Objectives
Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, ...and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.
Methods
Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18–90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank.
Results
No cross-sectional sleep—hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.
Conclusions
Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.
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.
Abstract
We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between ...self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18–92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. “PSQI # 1 Subjective sleep quality” and “PSQI #5 Sleep disturbances” were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with “PSQI #5 Sleep disturbances” emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
Abstract only Objective: Neuregulin-1 (Nrg1) promotes cardiomyocyte hypertrophy, survival, and cell cycle activity through ErbB signaling. It is investigated in clinical trials as a cardioprotective ...agent; however, its therapeutic use might be limited due to its pro-neoplastic potential for non-cardiomyocytes that makes targeted approaches necessary. High-throughput screening of hypertrophic agonists found that Nrg1 induces CITED4 (C4) expression. C4 is also upregulated in both physiological and pathological cardiac growth and necessary to prevent adverse remodeling in vivo. However, how C4 regulates Nrg1-signaling in the heart is yet unknown. Methods: We combined pulsed-SILAC labeling, click-chemistry and mass spectrometry that allows to capture immediate changes in the proteome and secretome after Nrg1 (12h and 24h) stimulation in siRNA-mediated C4-knockdown (C4KD) and control (ctr) NRVM and complemented this with established cell- and molecular biology techniques to validate and investigate cellular function and molecular signaling. Results: We confirmed dose-dependent C4 mRNA upregulation in response to Nrg1 stimulation in NRVM. Nrg1 downstream signaling through AKT was hindered in C4KD. Computational analysis comparing the nascent proteome after Nrg1 stimulation in C4KD and ctr NRVM revealed that C4 significantly regulates proteins responsible for translation, RNA processing and energy derivation. Consistent with previously observed development of cardiac fibrosis in C4 knockout mice in vivo , we found significant upregulation of TGFb2 in C4KD NRVM. We next confirmed the upregulation of TGFb2 and its downstream effectors in C4KD and ctr, while adenoviral overexpression of C4 led to reduced TGFb2 expression. Additionally, we found TGFb2 secretion increased from C4KD NRVM with Nrg1 stimulation in the nascent secretome. Conditioned media from C4KD NRVM led to an increased pro-fibrotic response in cardiac fibroblasts. In conclusion, nascent proteomics and secretomics help to elucidate C4-dependent Nrg1-signaling, which may be an important contribution toward our goal to identify targetable cardioprotective pathways in the heart.
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
Sub‐optimal classification, interpretation and response to intrapartum electronic fetal monitoring using cardiotocography are known problems. Training is often recommended as a solution, ...but there is lack of clarity about the effects of training and which type of training works best.
Objectives
Systematic review of the effects of training healthcare professionals in intrapartum cardiotocography (PROSPERO protocol: CRD42017064525).
Search strategy
CENTRAL, Cochrane Library, MEDLINE, EMBASE, PsycINFO, British Nursing Database, CINAHL, ERIC, Scopus, Web of Science, ProQuest, grey literature and ongoing clinical trials were searched.
Selection criteria
Primary studies that reported impact of training healthcare professionals in intrapartum cardiotocography. Title/, full‐text screening and quality assessment were conducted in duplicate.
Data collection and analysis
Data were synthesised both narratively and using meta‐analysis. Risk of bias and overall quality were assessed with the Mixed Methods Appraisal Tool and GRADE.
Main results
Sixty‐four studies were included. Overall, training and reporting were heterogeneous, the outcomes evaluated varied widely and study quality was low. Five randomised controlled trials reported that training improved knowledge of maternity professionals compared with no training, but evidence was of low quality. Evidence for the impact of cardiotocography training on neonatal and maternal outcomes was limited, showed inconsistent effects, and was of low overall quality. Evidence for the optimal content and method of delivery of training was very limited.
Conclusions
Given the scale of harm and litigation claims associated with electronic fetal monitoring, the evidence‐base for training requires improvement. It should address intervention design, evaluation of clinical outcomes and system‐wide contexts of sub‐optimal practice.
Tweetable
Training in fetal monitoring: systematic review finds little evidence of impact on neonatal outcomes.
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Training in fetal monitoring: systematic review finds little evidence of impact on neonatal outcomes.
Scientists' warning on invasive alien species Pyšek, Petr; Hulme, Philip E.; Simberloff, Dan ...
Biological reviews of the Cambridge Philosophical Society,
December 2020, Letnik:
95, Številka:
6
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Biological invasions are a global consequence of an increasingly connected world and the rise in human population size. The numbers of invasive alien species – the subset of alien species ...that spread widely in areas where they are not native, affecting the environment or human livelihoods – are increasing. Synergies with other global changes are exacerbating current invasions and facilitating new ones, thereby escalating the extent and impacts of invaders. Invasions have complex and often immense long‐term direct and indirect impacts. In many cases, such impacts become apparent or problematic only when invaders are well established and have large ranges. Invasive alien species break down biogeographic realms, affect native species richness and abundance, increase the risk of native species extinction, affect the genetic composition of native populations, change native animal behaviour, alter phylogenetic diversity across communities, and modify trophic networks. Many invasive alien species also change ecosystem functioning and the delivery of ecosystem services by altering nutrient and contaminant cycling, hydrology, habitat structure, and disturbance regimes. These biodiversity and ecosystem impacts are accelerating and will increase further in the future. Scientific evidence has identified policy strategies to reduce future invasions, but these strategies are often insufficiently implemented. For some nations, notably Australia and New Zealand, biosecurity has become a national priority. There have been long‐term successes, such as eradication of rats and cats on increasingly large islands and biological control of weeds across continental areas. However, in many countries, invasions receive little attention. Improved international cooperation is crucial to reduce the impacts of invasive alien species on biodiversity, ecosystem services, and human livelihoods. Countries can strengthen their biosecurity regulations to implement and enforce more effective management strategies that should also address other global changes that interact with invasions.
Background
Meadow ecosystems have important ecological functions and support socioeconomic services, yet are subject to multiple stressors that can lead to rapid degradation. In the Sierra Nevada of ...the western USA, recreational pack stock (horses and mules) use in seasonally wet mountain meadows may lead to soil trampling and meadow degradation, especially when soil water content is high and vegetation is developing.
Methods
In order to improve the ability to predict meadow vulnerability to soil disturbance from pack stock use, we measured soil resistance (SR), which is an index of vulnerability to trampling disturbance, at two spatial scales using a stratified-random sampling design. We then compared SR to several soil and vegetation explanatory variables that were also measured at the two spatial scales: plant community type (local scale) and topographic gradient class (meadow scale).
Results
We found that local-scale differences in drivers of SR were contingent on the meadow scale, which is important because multiple spatial scale evaluation of ecological metrics provides a broader understanding of the potential controls on ecological processes than assessments conducted at a single spatial scale. We also found two contrasting explanatory models for drivers of SR at the local scale: (1) soil gravimetric water content effects on soil disaggregation and (2) soil bulk density and root mass influence on soil cohesion. Soil resistance was insufficient to sustain pack stock use without incurring soil deformation in wet plant communities, even when plant cover was maximal during a major drought.
Conclusions
Our study provides new information on seasonally wet meadow vulnerability to trampling by pack stock animals using multi-scale drivers of SR, including the contrasting roles of soil disaggregation, friction, and cohesion. Our work aims to inform meadow management efforts in the Sierra Nevada and herbaceous ecosystems in similar regions that are subject to seasonal soil saturation and livestock use.
There is a lack of prospective data on the potential association of
(
) and colorectal cancer risk. In this study, we assessed whether antibody responses to
are associated with colorectal cancer risk ...in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort.
We applied a multiplex serology assay to simultaneously measure antibody responses to 11
antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).
We observed neither a statistically significant colorectal cancer risk association for antibodies to individual
proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62-1.06).
Antibody responses to
proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.
Our findings in prospectively ascertained serum samples contradict the existing literature on the association of
with colorectal cancer risk. Future prospective studies, specifically detecting
in stool or tissue biopsies, are needed to complement our findings.
Podocyte loss and changes to the complex morphology are major causes of chronic kidney disease (CKD). As the incidence is continuously increasing over the last decades without sufficient treatment, ...it is important to find predicting biomarkers. Therefore, we measured urinary mRNA levels of podocyte genes NPHS1, NPHS2, PODXL and BDNF, KIM‐1, CTSL by qRT‐PCR of 120 CKD patients. We showed a strong correlation between BDNF and the kidney injury marker KIM‐1, which were also correlated with NPHS1, suggesting podocytes as a contributing source. In human biopsies, BDNF was localized in the cell body and major processes of podocytes. In glomeruli of diabetic nephropathy patients, we found a strong BDNF signal in the remaining podocytes. An inhibition of the BDNF receptor TrkB resulted in enhanced podocyte dedifferentiation. The knockdown of the orthologue resulted in pericardial oedema formation and lowered viability of zebrafish larvae. We found an enlarged Bowman's space, dilated glomerular capillaries, podocyte loss and an impaired glomerular filtration. We demonstrated that BDNF is essential for glomerular development, morphology and function and the expression of BDNF and KIM‐1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential CKD biomarker.
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