These results indicate that the originality of CMDT is associated with (a) greater activation of the ventral attention system, which is involved in reorienting attention and (b) reduced task-induced deactivation of the default mode network, which is indicative of alterations in attentional reallocation, and (c) cognitive correlates of originality of CMDT and revealed sex differences in these associations. Differences in fMRI resting-state connectivity of the default mode network (DMN) seen in chronic pain patients are often interpreted as brain reorganization due to the chronic pain condition. Nevertheless, patients' pain at the time of fMRI might influence the DMN because pain, like cognitive stimuli, engages attentional mechanisms and cognitive engagement is known to alter DMN activity. Here, we aimed to dissociate the influence of chronic pain condition (trait) from the influence of current pain experience (state) on DMN connectivity in patients with fibromyalgia (FM). We performed resting-state fMRI scans to test DMN connectivity in FM patients and matched healthy controls in two separate cohorts (1) in a cohort not experiencing pain during scanning (27 FM patients and 27 controls), (2) in a cohort with current clinical pain during scanning (16 FM patients and 16 controls). In FM patients without pain during scanning, the connectivity of the DMN did not differ significantly from controls. By contrast, FM patients with current clinical pain during the scan had significantly increased DMN connectivity to bilateral anterior insula (INS) similar to previous studies. Regression analysis showed a positive relationship between DMN-midINS connectivity and current pain. We therefore suggest that transient DMN disruptions due to current clinical pain during scanning (current pain state) may be a substantial contributor to DMN connectivity disruptions observed in chronic pain patients. MRI has been widely used to probe the neuroanatomy of the mouse brain, directly correlating MRI findings to histology is still challenging due to the limited spatial resolution and various image contrasts derived from water relaxation or diffusion properties. Magnetic resonance histology has the potential to become an indispensable research tool to mitigate such challenges. In the present study, we acquired high spatial resolution MRI datasets, including diffusion MRI (dMRI) at 25 ​μm isotropic resolution and quantitative susceptibility mapping (QSM) at 21.5 ​μm isotropic resolution to validate with conventional mouse brain histology. Diffusion weighted images (DWIs) show better delineation of cortical layers and glomeruli in the olfactory bulb than fractional anisotropy (FA) maps. https://www.selleckchem.com/ However, among all the image contrasts, including quantitative susceptibility mapping (QSM), T1/T2∗ images and DTI metrics, FA maps highlight unique laminar architecture in sub-regions of the hippocampus, including the strata of the dentate gyrus and CA fields of the hippocampus. The mean diffusivity (MD) and axial diffusivity (AD) yield higher correlation with DAPI (0.62 and 0.71) and NeuN (0.78 and 0.74) than with NF-160 (-0.34 and -0.49). The correlations between FA and DAPI, NeuN, and NF-160 are 0.31, -0.01, and -0.49, respectively. Our findings demonstrate that MRI at microscopic resolution deliver a three-dimensional, non-invasive and non-destructive platform for characterization of fine structural detail in both gray matter and white matter of the mouse brain. BACKGROUND CONTEXT Small leucine-rich proteoglycans (SLRPs) play an essential role in ECM organization and function. Recently, dysregulation of SLRPs has been implicated in degenerative disc disease (DDD). An in-depth analysis using high-throughput proteomic sequencing might provide valuable information on their implications in health and disease. PURPOSE To utilize proteomics for analyzing the expression of SLRPs in fetal, healthy adult and degenerated discs, to identify possible molecular targets to halt or reverse the degenerative process. STUDY DESIGN Experimental analysis METHODS Proteomic signatures of eight MRI normal lumbar discs (ND) [harvested from brain dead alive organ donors] were compared to eight fetal disc samples (FD) [harvested from fetal spines devoid of congenital anomalies following spontaneous or medical termination of pregnancy] and eight degenerate discs (DD) [collected from patients undergoing fusion surgery]. The various functional pathways along with the differential expression of SDDD. Analysis of SLRPs revealed the upregulation of Biglycan in fetal discs and downregulation of Lumican, Decorin, Prolargin and Chondroadherin in the DD group. The universal decrease in the abundance of SLRPs in the DD group was associated with an increase in MMPs and a reduction in TIMPs, collagen and LLRP content. CONCLUSION Our study documents the influence of SLRPs in the maintenance of disc health and also the need for future research in using them for disc regeneration. BACKGROUND Tocopherol isoforms may regulate child lung growth and spirometric measures. OBJECTIVE To determine the extent to which plasma alpha (α-T) or gamma tocopherol (γ-T) isoform levels in early childhood or in-utero are associated with childhood lung function. METHODS We included 622 participants in the Project Viva cohort, who had lung function at a mid-childhood visit (age 6-10 years old). Maternal and child tocopherol isoform levels were measured by HPLC at second trimester and 3 years old, respectively. Multivariable linear regression models (adjusted for mid-childhood BMI-z-scores, and maternal education, smoking in pregnancy, and prenatal PM2.5 particulate exposure), stratified by tertiles of child γ-T, were employed to assess the association of α-T levels with FEV1 and FVC percent predicted. Similarly, models stratified by child α-T tertile evaluated associations of γ-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels. RESULTS The maternal second trimester α-T level was median;IQR 63; 47-82 μM. The early childhood levels were median;IQR 25; 20-33 μM. In the lowest tertile of early childhood γ-T, children with higher α-T levels (per 10 μM) had higher mid-childhood FEV1 %-predicted (β=3.09, 95%CI=0.58-5.59), and a higher FVC %-predicted (β=2.77, 95%CI=0.47,5.06). This protective association of α-T was lost at higher γ-T levels. We did not see any consistent associations of second trimester levels of either α-T or γ-T with mid-childhood FEV1 or FVC. CONCLUSION When γ-T levels were in the lowest tertile, higher early childhood α-T was associated with better lung function at mid-childhood. Second trimester maternal plasma α-T concentration was 3-fold higher than the adult female non-pregnant population. CLINICAL IMPLICATION α-Tocopherol and γ-tocopherol isoforms are potentially modifiable exposures that have differential associations with lung function in later childhood.