Data-driven MRI analysis reveals fitness-related functional change in default mode network and cognition following an exercise intervention

Previous research has indicated that cardiorespiratory fitness (CRF) is structurally and functionally neuroprotective in older adults. However, questions remain regarding the mechanistic role of CRF on cognitive and brain health. The purposes of this study were to investigate if higher pre-intervention CRF was associated with greater change in functional brain connectivity during an exercise intervention and to determine if the magnitude of change in connectivity was related to better post-intervention cognitive performance. The sample included low-active older adults (n = 139) who completed a 6-month exercise intervention and underwent neuropsychological testing, functional neuroimaging, and CRF testing before and after the intervention. A data-driven multi-voxel pattern analysis was performed on resting-state MRI scans to determine changes in whole-brain patterns of connectivity from pre- to post-intervention as a function of pre-intervention CRF. Results revealed a positive correlation between pre-intervention CRF and changes in functional connectivity in the precentral gyrus. Using the precentral gyrus as a seed, analyses indicated that CRF-related connectivity changes within the precentral gyrus were derived from increased correlation strength within clusters located in the Dorsal Attention Network (DAN) and increased anti-correlation strength within clusters located in the Default Mode Network (DMN). Exploratory analysis demonstrated that connectivity change between the precentral gyrus seed and DMN clusters were associated with improved post-intervention performance on perceptual speed tasks. These findings suggest that in a sample of low-active and mostly lower-fit older adults, even subtle individual differences in CRF may influence the relationship between functional connectivity and aspects of cognition following a 6-month exercise intervention.Center for Nutrition, Learning, and Memory at University of Illinois, Grant/Award Number: C4712National Institute on Aging, Grant/Award Number: R37 AG02566

Increased Responsiveness to Novelty is Associated with Successful Cognitive Aging

The animal literature suggests that exposure to more complex, novel environments promotes neurogenesis and cognitive performance in older animals. Studies in humans indicate that participation in intellectually stimulating activities may serve as a buffer against mental decline and help to sustain cognitive abilities. Here, we show that across old adults, increased responsiveness to novel events (as measured by viewing duration and the size of the P3 event-related potential) is strongly linked to better performance on neuropsychological tests, especially those involving attention/executive functions. Cognitively high performing old adults generate a larger P3 response to visual stimuli than cognitively average performing adults. These results suggest that cognitively high performing adults successfully manage the task by appropriating more resources and that the increased size of their P3 component represents a beneficial compensatory mechanism rather than less efficient processing

Why do models overestimate surface ozone in the Southeast United States

Ozone pollution in the Southeast US involves complex chemistry driven by emissions of anthropogenic nitrogen oxide radicals (NOx  ≡  NO + NO2) and biogenic isoprene. Model estimates of surface ozone concentrations tend to be biased high in the region and this is of concern for designing effective emission control strategies to meet air quality standards. We use detailed chemical observations from the SEAC4RS aircraft campaign in August and September 2013, interpreted with the GEOS-Chem chemical transport model at 0.25°  ×  0.3125° horizontal resolution, to better understand the factors controlling surface ozone in the Southeast US. We find that the National Emission Inventory (NEI) for NOx from the US Environmental Protection Agency (EPA) is too high. This finding is based on SEAC4RS observations of NOx and its oxidation products, surface network observations of nitrate wet deposition fluxes, and OMI satellite observations of tropospheric NO2 columns. Our results indicate that NEI NOx emissions from mobile and industrial sources must be reduced by 30–60 %, dependent on the assumption of the contribution by soil NOx emissions. Upper-tropospheric NO2 from lightning makes a large contribution to satellite observations of tropospheric NO2 that must be accounted for when using these data to estimate surface NOx emissions. We find that only half of isoprene oxidation proceeds by the high-NOx pathway to produce ozone; this fraction is only moderately sensitive to changes in NOx emissions because isoprene and NOx emissions are spatially segregated. GEOS-Chem with reduced NOx emissions provides an unbiased simulation of ozone observations from the aircraft and reproduces the observed ozone production efficiency in the boundary layer as derived from a regression of ozone and NOx oxidation products. However, the model is still biased high by 6 ± 14 ppb relative to observed surface ozone in the Southeast US. Ozonesondes launched during midday hours show a 7 ppb ozone decrease from 1.5 km to the surface that GEOS-Chem does not capture. This bias may reflect a combination of excessive vertical mixing and net ozone production in the model boundary layer

In Vivo Flow Dynamics of the Total Cavopulmonary Connection from Three-dimensional Multislice Magnetic Resonance Imaging

Background. The total cavopulmonary connection (TCPC) design continues to be refined on the basis of flow analysis at the connection site. These refinements are of importance for myocardial energy conservation in the univentricular supported circulation. In vivo magnetic resonance phase contrast imaging provides semiquantitative flow visualization information. The purpose of this study was to understand the in vivo TCPC flow characteristics obtained by magnetic resonance phase contrast imaging and compare the results with our previous in vitro TCPC flow experiments in an effort to further refine TCPC surgical design. Methods. Twelve patients with TCPC underwent sedated three-dimensional, multislice magnetic resonance phase contrast imaging. Seven patients had intraatrial lateral tunnel TCPC and 5 had extracardiac TCPC. Results. In all patients in both groups a disordered flow pattern was observed in the inferior caval portion of the TCPC. Flow at the TCPC site appeared to be determined by connection geometry, being streamlined at the superior vena cava–pulmonary junction when the superior vena cava was offset and flared toward the left pulmonary artery. Without caval offset, intense swirling and dominance of superior vena caval flow was observed. In TCPC with bilateral superior vena cavae, the flow patterns observed included secondary vortices, a central stagnation point, and influx of the superior vena cava flow into the inferior caval conduit. A comparative analysis of in vivo flow and our previous in vitro flow data from glass model prototypes of TCPC demonstrated significant similarities in flow disturbances. Three-dimensional magnetic resonance phase contrast imaging in multiple coronal planes enabled a comprehensive semiquantitative flow analysis. The data are presented in traditional instantaneous images and in animated format for interactive display of the flow dynamics. Conclusions. Flow in the inferior caval portion of the TCPC is disordered, and the TCPC geometry determines flow characteristics

Primary Caregivers of Children Affected by Disorders of Sex Development: Mental Health and Caregiver Characteristics in the Context of Genital Ambiguity and Genitoplasty

Purpose. To determine the relationship between having a child with a DSD including ambiguous external genitalia, as well as the decision of whether or not to have early genitoplasty for that child, on the mental health and parenting characteristics of caregivers. Materials and Methods. Caregivers were recruited from centers that specialize in DSD medicine and completed the Beck Depression Inventory 2nd Edition (BDI-2), Beck Anxiety Index (BAI), Parent Protection Scale (PPS), Child Vulnerability Scale (CVS) and Parenting Stress Index/Short Form (PSI/SF). Results and Conclusions. Sixty-eight caregivers provided informed consent and completed the study. Among female caregivers whose children never received genitoplasty, greater parenting stress was reported (F(1, 40) = 5.08, p = .03). For male caregivers, those whose children received genitoplasty within the first year of life reported more overprotective parenting and parenting stress than those whose children received genitoplasty later than 12 months of age (F(1, 13) = 6.16, p = 0.28); F(1, 15) = 6.70, p = .021), respectively)

In Vivo Flow Dynamics of the Total Cavopulmonary Connection from Three-dimensional Multislice Magnetic Resonance Imaging

Background. The total cavopulmonary connection (TCPC) design continues to be refined on the basis of flow analysis at the connection site. These refinements are of importance for myocardial energy conservation in the univentricular supported circulation. In vivo magnetic resonance phase contrast imaging provides semiquantitative flow visualization information. The purpose of this study was to understand the in vivo TCPC flow characteristics obtained by magnetic resonance phase contrast imaging and compare the results with our previous in vitro TCPC flow experiments in an effort to further refine TCPC surgical design. Methods. Twelve patients with TCPC underwent sedated three-dimensional, multislice magnetic resonance phase contrast imaging. Seven patients had intraatrial lateral tunnel TCPC and 5 had extracardiac TCPC. Results. In all patients in both groups a disordered flow pattern was observed in the inferior caval portion of the TCPC. Flow at the TCPC site appeared to be determined by connection geometry, being streamlined at the superior vena cava–pulmonary junction when the superior vena cava was offset and flared toward the left pulmonary artery. Without caval offset, intense swirling and dominance of superior vena caval flow was observed. In TCPC with bilateral superior vena cavae, the flow patterns observed included secondary vortices, a central stagnation point, and influx of the superior vena cava flow into the inferior caval conduit. A comparative analysis of in vivo flow and our previous in vitro flow data from glass model prototypes of TCPC demonstrated significant similarities in flow disturbances. Three-dimensional magnetic resonance phase contrast imaging in multiple coronal planes enabled a comprehensive semiquantitative flow analysis. The data are presented in traditional instantaneous images and in animated format for interactive display of the flow dynamics. Conclusions. Flow in the inferior caval portion of the TCPC is disordered, and the TCPC geometry determines flow characteristics

Characterization of the ATP4 ion pump in Toxoplasma gondii

The Plasmodium falciparum ATPase PfATP4 is the target of a diverse range of antimalarial compounds, including the clinical drug candidate cipargamin. PfATP4 was originally annotated as a Ca2+ transporter, but recent evidence suggests that it is a Na+ efflux pump, extruding Na+ in exchange for H+. Here we demonstrate that ATP4 proteins belong to a clade of P-type ATPases that are restricted to apicomplexans and their closest relatives. We employed a variety of genetic and physiological approaches to investigate the ATP4 protein of the apicomplexan Toxoplasma gondii, TgATP4. We show that TgATP4 is a plasma membrane protein. Knockdown of TgATP4 had no effect on resting pH or Ca2+ but rendered parasites unable to regulate their cytosolic Na+ concentration ([Na+]cyt). PfATP4 inhibitors caused an increase in [Na+]cyt and a cytosolic alkalinization in WT but not TgATP4 knockdown parasites. Parasites in which TgATP4 was knocked down or disrupted exhibited a growth defect, attributable to reduced viability of extracellular parasites. Parasites in which TgATP4 had been disrupted showed reduced virulence in mice. These results provide evidence for ATP4 proteins playing a key conserved role in Na+ regulation in apicomplexan parasites.This work was supported by National Health and Medical Research Council Grant 1042272 (to K. K.) and Australian Research Council Discovery Project Grant DP150102883 (to K. K. and G. G. v. D.), Linkage Project Grant LP150101226 (to K. K.), Discovery Early Career Researcher Award DE160101035 (to A. M. L.), QEII Fellowship DP110103144 (to G. G. v. D.), and Future Fellowship FT120100164 (to C. J. T.). C. J. T. is grateful for institutional support from the Victorian State Government Operational Infrastructure Support Program and the National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme