The Relationship Between Early Life Stress and Microstructural Integrity of the Corpus Callosum in a Non-Clinical Population

Background: Previous studies have examined the impact of early life stress (ELS) on the gross morphometry of brain regions, including the corpus callosum. However, studies have not examined the relationship between ELS and the microstructural integrity of the brain. Previous studies have examined the impact of early life stress (ELS) on the gross morphometry of brain regions, including the corpus callosum. However, studies have not examined the relationship between ELS and the microstructural integrity of the brain. Methods: In the present study we evaluated this relationship in healthy non-clinical participants using diffusion tensor imaging (DTI) and self-reported history of ELS. Results: Regression analyses revealed significant reductions in fractional anisotropy (FA) within the genu of the corpus callosum among those exposed to the greatest number of early life stressors, suggesting reduced microstructural integrity associated with increased ELS. These effects were most pronounced in the genu of the corpus callosum compared to the body and splenium, and were evident for females rather than males despite no differences in total ELS exposure between the sexes. In addition, a further comparison of those participants who were exposed to no ELS vs. three or more ELS events revealed lower FA in the genu of the corpus callosum among the ELS-exposed group, with trends of FA reduction in the body and the whole corpus callosum. By contrast, there were no relationships between ELS and volumetric analysis of the CC regions. The two group did not differ significantly on measures of current depression, stress or anxiety. Conclusion: Our results reveal that greater exposure to ELS is associated with microstructural alterations in the white matter in the absence of significant volumetric changes. Importantly, our results indicate that exposure to ELS is associated with abnormalities on DTI despite the absence of clinically significant psychiatric symptoms. Future studies are needed to determine whether specific types of ELS are more likely to impact brain structure and function

Brain Volumetrics, Regional Cortical Thickness and Radiographic Findings in Adults with Cyanotic Congenital Heart Disease

AbstractBackgroundChronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized.HypothesisWe hypothesized that adults with cyanotic CHD would have widespread changes including abnormal brain volumetric measures, decreased cortical thickness and an increased burden of small and large vessel ischemic changes.MethodsTen adults with chronic cyanosis from CHD (40±4years) and mean oxygen saturations of 82±2% were investigated using quantitative MRI. Hematological and biochemical parameters were also assessed. All subjects were free from major physical or intellectual impairment. Brain volumetric results were compared with randomly selected age- and sex-matched controls from our database of normal subjects.ResultsFive of 10 cyanotic subjects had cortical lacunar infarcts. The white matter (WM) hyperintensity burden was also abnormally high (Scheltens Scale was 8±2). Quantitative MRI revealed evidence of extensive generalized WM and gray matter (GM) volumetric loss; global GM volume was reduced in cyanosed subjects (630±16 vs. 696±14mL in controls, p=0.01) as was global WM volume (471±10 vs. 564±18mL, p=0.003). Ventricular cerebrospinal fluid volume was increased (35±10 vs. 26±5mL, p=0.002). There were widespread regions of local cortical thickness reduction observed across the brain. These changes included bilateral thickness reductions in the frontal lobe including the dorsolateral prefrontal cortex and precentral gyrus, the posterior parietal lobe and the middle temporal gyrus. Sub-cortical volume changes were observed in the caudate, putamen and in the thalamus (p≤0.005 for all regions). Cortical GM volume negatively correlated with brain natriuretic peptide (R=−0.89, p=0.009), high sensitivity C-reactive protein (R=−0.964, p<0.0001) and asymmetric dimethylarginine (R=−0.75, p=0.026) but not with oxygen saturations, packed cell volume or viscosity.ConclusionsWe present the first comprehensive analysis of brain structure in adults with chronic neurocyanosis due to congenital heart disease. We demonstrate clear evidence for marked macro- and microvascular injury. Cyanotic patients show global evidence for reduced brain volume as well as specific foci of cortical thickness reduction. The GM volume loss correlated with hsCRP, BNP and ADMA suggesting that inflammation, neurohormonal activation and endothelial dysfunction may have important roles in its pathogenesis

Hippocampal volume varies with educational attainment across the life-span

Socioeconomic disparities—and particularly differences in educational attainment—are associated with remarkable differences in cognition and behavior across the life-span. Decreased educational attainment has been linked to increased exposure to life stressors, which in turn have been associated with structural differences in the hippocampus and the amygdala. However, the degree to which educational attainment is directly associated with anatomical differences in these structures remains unclear. Recent studies in children have found socioeconomic differences in regional brain volume in the hippocampus and amygdala across childhood and adolescence. Here we expand on this work, by investigating whether disparities in hippocampal and amygdala volume persist across the life-span. In a sample of 275 individuals from the BRAINnet Foundation database ranging in age from 17 to 87, we found that socioeconomic status (SES), as operationalized by years of educational attainment, moderates the effect of age on hippocampal volume. Specifically, hippocampal volume tended to markedly decrease with age among less educated individuals, whereas age-related reductions in hippocampal volume were less pronounced among more highly educated individuals. No such effects were found for amygdala volume. Possible mechanisms by which education may buffer age-related effects on hippocampal volume are discussed

A nondimensional framework for exploring the relief structure of landscapes

Considering the relationship between erosion rate and the relief structure of a landscape within a nondimensional framework facilitates the comparison of landscapes undergoing forcing at a range of scales, and allows broad-scale patterns of landscape evolution to be observed. We present software which automates the extraction and processing of relevant topographic parameters to rapidly generate nondimensional erosion rate and relief data for any landscape where high-resolution topographic data are available. Individual hillslopes are identified using a connected-components technique which allows spatial averaging to be performed over geomorphologically meaningful spatial units, without the need for manual identification of hillslopes. The software is evaluated on four landscapes across the continental United States, three of which have been studied previously using this technique. We show that it is possible to identify whether landscapes are in topographic steady state. In locations such as Cascade Ridge, CA, a clear signal of an erosional gradient can be observed. In the southern Appalachians, nondimensional erosion rate and relief data are interpreted as evidence for a landscape decaying following uplift during the Miocene. An analysis of the sensitivity of this method to free parameters used in the data smoothing routines is presented which allows users to make an informed choice of parameters when interrogating new topographic data using this method. A method to constrain the critical gradient of the nonlinear sediment flux law is also presented which provides an independent constraint on this parameter for three of the four study landscapes

Evidence for coeval Late Triassic terrestrial impacts from the Rochechouart (France) meteorite crater

High temperature impact melt breccias from the Rochechouart (France) meteorite crater record magnetization component with antipodal, normal and reverse polarities. The corresponding paleomagnetic pole for this component lies between the 220 Ma and 210 Ma reference poles on the Eurasian apparent polar wander path, consistent with the 214 $\pm$ 8 Ma 40Ar/39Ar age of the crater. Late Triassic tectonic reconstructions of the Eurasian and North American plates place this pole within 95% confidence limits of the paleomagnetic pole from the Manicouagan (Canada) meteorite impact crater, which is dated at 214 $\pm$ 1 Ma. Together, these observations reinforce the hypothesis of a Late Triassic, multiple meteorite impact event on Earth

The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population

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[Ni(NHC)2] as a scaffold for structurally characterized trans [H-Ni-PR2] and trans [R2P-Ni-PR2] complexes

The addition of PPh2H, PPhMeH, PPhH2, P(para-Tol)H2, PMesH2 and PH3 to the two-coordinate Ni0 N-heterocyclic carbene species [Ni(NHC)2] (NHC=IiPr2, IMe4, IEt2Me2) affords a series of mononuclear, terminal phosphido nickel complexes. Structural characterisation of nine of these compounds shows that they have unusual trans [H−Ni−PR2] or novel trans [R2P−Ni−PR2] geometries. The bis-phosphido complexes are more accessible when smaller NHCs (IMe4&gt;IEt2Me2&gt;IiPr2) and phosphines are employed. P−P activation of the diphosphines R2P−PR2 (R2=Ph2, PhMe) provides an alternative route to some of the [Ni(NHC)2(PR2)2] complexes. DFT calculations capture these trends with P−H bond activation proceeding from unconventional phosphine adducts in which the H substituent bridges the Ni−P bond. P−P bond activation from [Ni(NHC)2(Ph2P−PPh2)] adducts proceeds with computed barriers below 10 kcal mol−1. The ability of the [Ni(NHC)2] moiety to afford isolable terminal phosphido products reflects the stability of the Ni−NHC bond that prevents ligand dissociation and onward reaction

[Ni(NHC)2] as a scaffold for structurally characterized trans [H-Ni-PR2] and trans [R2P-Ni-PR2] complexes

The addition of PPh(2)H, PPhMeH, PPhH(2), P(para‐Tol)H(2), PMesH(2) and PH(3) to the two‐coordinate Ni(0) N‐heterocyclic carbene species [Ni(NHC)(2)] (NHC=IiPr(2), IMe(4), IEt(2)Me(2)) affords a series of mononuclear, terminal phosphido nickel complexes. Structural characterisation of nine of these compounds shows that they have unusual trans [H−Ni−PR(2)] or novel trans [R(2)P−Ni−PR(2)] geometries. The bis‐phosphido complexes are more accessible when smaller NHCs (IMe(4)>IEt(2)Me(2)>IiPr(2)) and phosphines are employed. P−P activation of the diphosphines R(2)P−PR(2) (R(2)=Ph(2), PhMe) provides an alternative route to some of the [Ni(NHC)(2)(PR(2))(2)] complexes. DFT calculations capture these trends with P−H bond activation proceeding from unconventional phosphine adducts in which the H substituent bridges the Ni−P bond. P−P bond activation from [Ni(NHC)(2)(Ph(2)P−PPh(2))] adducts proceeds with computed barriers below 10 kcal mol(−1). The ability of the [Ni(NHC)(2)] moiety to afford isolable terminal phosphido products reflects the stability of the Ni−NHC bond that prevents ligand dissociation and onward reaction

Longer-term oral antiplatelet use in stable post-myocardial infarction patients: Insights from the long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease (TIGRIS) observational study.

OBJECTIVE: To describe contemporary patient characteristics and treatment patterns, including antithrombotic management, of post-myocardial infarction (MI) stable coronary artery disease (CAD) patients at high atherothrombotic risk from different geographical regions. METHODS: Patients ≥50years with prior MI 1-3years ago and ≥1 risk factor (age ≥65years, diabetes, 2nd prior MI >1yr ago, multivessel CAD, creatinine clearance 15-1year was highest (39%) in Asia-Pacific and lowest (12%) in Europe. CONCLUSIONS: Despite guideline recommendations, 1 in 4 post-MI patients did not receive DAPT for ~1year. In contrast to guideline recommendations supporting newer ADPris, clopidogrel was mainly prescribed. Prior to recent RCT data supporting DAPT >1year post-MI/PCI, >1 in 4 patients have continued on DAPT, though with substantial international variability