Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

GARFIELD-AF: risk profiles, treatment patterns and 2-year outcomes in patients with atrial fibrillation in Germany, Austria and Switzerland (DACH) compared to 32 countries in other regions worldwide.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with non-valvular AF. METHODS AND RESULTS: 52,080 patients with newly diagnosed AF were prospectively enrolled from 2010 to 2016. 4121 (7.9%) of these patients were recruited in DACH [Germany (n = 3567), Austria (n = 465) and Switzerland (n = 89) combined], and 47,959 patients were from 32 countries in other regions worldwide (ORW). Hypertension was most prevalent in DACH and ORW (85.3% and 75.6%, respectively). Diabetes, hypercholesterolaemia, carotid occlusive disease and vascular disease were more prevalent in DACH patients vs ORW (27.6%, 49.4%, 5.8% and 29.0% vs 21.7%, 40.9%, 2.8% and 24.5%). The use of non-vitamin K antagonist oral anticoagulants (NOACs) increased more in DACH over time. Management of vitamin K antagonists was suboptimal in DACH and ORW (time in therapeutic range of INR ≥ 65% in 44.6% and 44.4% of patients or ≥ 70% in 36.9% and 36.0% of patients, respectively). Adjusted rates of cardiovascular mortality and MI/ACS were higher in DACH while non-haemorrhagic stroke/systemic embolism was lower after 2-year follow-up. CONCLUSIONS: Similarities and dissimilarities in AF management and clinical outcomes are seen in DACH and ORW. The increased use of NOAC was associated with a mismatch of risk-adapted anticoagulation (over-and-undertreatment) in DACH. Suboptimal control of INR requires educational activities in both regional groups. Higher rates of cardiovascular death in DACH may reflect the higher risk profile of these patients and lower rates of non-haemorrhagic stroke could be associated with increased NOAC use

LRP1 Regulates Architecture of the Vascular Wall by Controlling PDGFRβ-Dependent Phosphatidylinositol 3-Kinase Activation

Low density lipoprotein receptor-related protein 1 (LRP1) protects against atherosclerosis by regulating the activation of platelet-derived growth factor receptor beta (PDGFRbeta) in vascular smooth muscle cells (SMCs). Activated PDGFRbeta undergoes tyrosine phosphorylation and subsequently interacts with various signaling molecules, including phosphatidylinositol 3-kinase (PI3K), which binds to the phosphorylated tyrosine 739/750 residues in mice, and thus regulates actin polymerization and cell movement.In this study, we found disorganized actin in the form of membrane ruffling and enhanced cell migration in LRP1-deficient (LRP1-/-) SMCs. Marfan syndrome-like phenotypes such as tortuous aortas, disrupted elastic layers and abnormally activated transforming growth factor beta (TGFbeta) signaling are present in smooth muscle-specific LRP1 knockout (smLRP1-/-) mice. To investigate the role of LRP1-regulated PI3K activation by PDGFRbeta in atherogenesis, we generated a strain of smLRP1-/- mice in which tyrosine 739/750 of the PDGFRbeta had been mutated to phenylalanines (PDGFRbeta F2/F2). Spontaneous atherosclerosis was significantly reduced in the absence of hypercholesterolemia in these mice compared to smLRP1-/- animals that express wild type PDGFR. Normal actin organization was restored and spontaneous SMC migration as well as PDGF-BB-induced chemotaxis was dramatically reduced, despite continued overactivation of TGFbeta signaling, as indicated by high levels of nuclear phospho-Smad2.Our data suggest that LRP1 regulates actin organization and cell migration by controlling PDGFRbeta-dependent activation of PI3K. TGFbeta activation alone is not sufficient for the expression of the Marfan-like vascular phenotype. Thus, regulation of PI3 Kinase by PDGFRbeta is essential for maintaining vascular integrity, and for the prevention of atherosclerosis as well as Marfan syndrome

In Vivo Mapping of Vascular Inflammation Using Multimodal Imaging

Plaque vulnerability to rupture has emerged as a critical correlate to risk of adverse coronary events but there is as yet no clinical method to assess plaque stability in vivo. In the search to identify biomarkers of vulnerable plaques an association has been found between macrophages and plaque stability--the density and pattern of macrophage localization in lesions is indicative of probability to rupture. In very unstable plaques, macrophages are found in high densities and concentrated in the plaque shoulders. Therefore, the ability to map macrophages in plaques could allow noninvasive assessment of plaque stability. We use a multimodality imaging approach to noninvasively map the distribution of macrophages in vivo. The use of multiple modalities allows us to combine the complementary strengths of each modality to better visualize features of interest. Our combined use of Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) allows high sensitivity PET screening to identify putative lesions in a whole body view, and high resolution MRI for detailed mapping of biomarker expression in the lesions.Macromolecular and nanoparticle contrast agents targeted to macrophages were developed and tested in three different mouse and rat models of atherosclerosis in which inflamed vascular plaques form spontaneously and/or are induced by injury. For multimodal detection, the probes were designed to contain gadolinium (T1 MRI) or iron oxide (T2 MRI), and Cu-64 (PET). PET imaging was utilized to identify regions of macrophage accumulation; these regions were further probed by MRI to visualize macrophage distribution at high resolution. In both PET and MR images the probes enhanced contrast at sites of vascular inflammation, but not in normal vessel walls. MRI was able to identify discrete sites of inflammation that were blurred together at the low resolution of PET. Macrophage content in the lesions was confirmed by histology.The multimodal imaging approach allowed high-sensitivity and high-resolution mapping of biomarker distribution and may lead to a clinical method to predict plaque probability to rupture

Impaired Ca2+-handling in HIF-1α+/− mice as a consequence of pressure overload

The hypoxia-inducible factor (HIF)-1 is critically involved in the cellular adaptation to a decrease in oxygen availability. The influence of HIF-1α for the development of cardiac hypertrophy and cardiac function that occurs in response to sustained pressure overload has been mainly attributed to a challenged cardiac angiogenesis and cardiac hypertrophy up to now. Hif-1α+/+ and Hif-1α+/− mice were studied regarding left ventricular hypertrophy and cardiac function after being subjected to transverse aortic constriction (TAC). After TAC, both Hif-1α+/+ and Hif-1α+/− mice developed left ventricular hypertrophy with increased posterior wall thickness, septum thickness and increased left ventricular weight to a similar extent. No significant difference in cardiac vessel density was observed between Hif-1α+/+ and Hif-1α+/− mice. However, only the Hif-1α+/− mice developed severe heart failure as revealed by a significantly reduced fractional shortening mostly due to increased end-systolic left ventricular diameter. On the single cell level this correlated with reduced myocyte shortenings, decreased intracellular Ca2+-transients and SR-Ca2+ content in myocytes of Hif-1a+/− mice. Thus, HIF-1α can be critically involved in the preservation of cardiac function after chronic pressure overload without affecting cardiac hypertrophy. This effect is mediated via HIF-dependent modulation of cardiac calcium handling and contractility

Kinesiophobia in patients with non-traumatic arm, neck and shoulder complaints: a prospective cohort study in general practice

BACKGROUND: Complaints of arm, neck and shoulder are common in Western societies. Of those consulting a general practitioner (GP) with non-traumatic arm, neck or shoulder complaints, about 50% do not recover within 6 months.Kinesiophobia (also known as fear of movement/(re)injury) may also play a role in these complaints, as it may lead to avoidance behaviour resulting in hypervigilance to bodily sensations, followed by disability, disuse and depression. However, in relation to arm, neck and shoulder complaints little is known about kinesiophobia and its associated variables.Therefore this study aimed to: describe the degree of kinesiophobia in patients with non-traumatic complaints of arm, neck and shoulder in general practice; to determine whether mean scores of kinesiophobia change over time in non-recovered patients; and to evaluate variables associated with kinesiophobia at baseline. METHODS: In this prospective cohort study set in general practice, consulters with a first or new episode of non-traumatic arm, neck or shoulder complaints (aged 18-64 years) entered the cohort. Baseline data were collected on kinesiophobia using the Tampa Scale for Kinesiophobia, the 13-item adjusted version: TSK-AV, and on patient-, complaint-, and psychosocial variables using self-administered questionnaires. The mean TSK-AV score was calculated. In non-recovered patients the follow-up TSK-AV scores at 6 and 12 months were analyzed with the general linear mixed model. Variables associated with kinesiophobia at baseline were evaluated using multivariate linear regression analyses. RESULTS: The mean TSK-AV score at baseline was 24.8 [SD: 6.2]. Among non-recovered patients the mean TSK-AV score at baseline was 26.1 [SD: 6.6], which remained unchanged over 12- months follow-up period. The strongest associations with kinesiophobia were catastrophizing, disability, and comorbidity of musculoskeletal complaints. Additionally, having a shoulder complaint, low social support, high somatization and high distress contributed to the kinesiophobia score. CONCLUSION: The mean TSK-AV score in our population seems comparable to those in other populations in primary care.In patients who did not recover during the 12- month follow-up, the degree of kinesiophobia remained unchanged during this time period.The variables associated with kinesiophobia at baseline appear to be in line with the fear-avoidance model

Explicit attention interferes with selective emotion processing in human extrastriate cortex

BACKGROUND: Brain imaging and event-related potential studies provide strong evidence that emotional stimuli guide selective attention in visual processing. A reflection of the emotional attention capture is the increased Early Posterior Negativity (EPN) for pleasant and unpleasant compared to neutral images (~150–300 ms poststimulus). The present study explored whether this early emotion discrimination reflects an automatic phenomenon or is subject to interference by competing processing demands. Thus, emotional processing was assessed while participants performed a concurrent feature-based attention task varying in processing demands. RESULTS: Participants successfully performed the primary visual attention task as revealed by behavioral performance and selected event-related potential components (Selection Negativity and P3b). Replicating previous results, emotional modulation of the EPN was observed in a task condition with low processing demands. In contrast, pleasant and unpleasant pictures failed to elicit increased EPN amplitudes compared to neutral images in more difficult explicit attention task conditions. Further analyses determined that even the processing of pleasant and unpleasant pictures high in emotional arousal is subject to interference in experimental conditions with high task demand. Taken together, performing demanding feature-based counting tasks interfered with differential emotion processing indexed by the EPN. CONCLUSION: The present findings demonstrate that taxing processing resources by a competing primary visual attention task markedly attenuated the early discrimination of emotional from neutral picture contents. Thus, these results provide further empirical support for an interference account of the emotion-attention interaction under conditions of competition. Previous studies revealed the interference of selective emotion processing when attentional resources were directed to locations of explicitly task-relevant stimuli. The present data suggest that interference of emotion processing by competing task demands is a more general phenomenon extending to the domain of feature-based attention. Furthermore, the results are inconsistent with the notion of effortlessness, i.e., early emotion discrimination despite concurrent task demands. These findings implicate to assess the presumed automatic nature of emotion processing at the level of specific aspects rather than considering automaticity as an all-or-none phenomenon

Specific bottom–up effects of arbuscular mycorrhizal fungi across a plant–herbivore–parasitoid system

The majority of plants are involved in symbioses with arbuscular mycorrhizal fungi (AMF), and these associations are known to have a strong influence on the performance of both plants and insect herbivores. Little is known about the impact of AMF on complex trophic chains, although such effects are conceivable. In a greenhouse study we examined the effects of two AMF species, Glomus intraradices and G. mosseae on trophic interactions between the grass Phleum pratense, the aphid Rhopalosiphum padi, and the parasitic wasp Aphidius rhopalosiphi. Inoculation with AMF in our study system generally enhanced plant biomass (+5.2%) and decreased aphid population growth (−47%), but there were no fungal species-specific effects. When plants were infested with G. intraradices, the rate of parasitism in aphids increased by 140% relative to the G. mosseae and control treatment. When plants were associated with AMF, the developmental time of the parasitoids decreased by 4.3% and weight at eclosion increased by 23.8%. There were no clear effects of AMF on the concentration of nitrogen and phosphorus in plant foliage. Our study demonstrates that the effects of AMF go beyond a simple amelioration of the plants’ nutritional status and involve rather more complex species-specific cascading effects of AMF in the food chain that have a strong impact not only on the performance of plants but also on higher trophic levels, such as herbivores and parasitoids