Search

The hierarchical modular organization of functional networks in the brain is crucial for supporting diverse cognitive functions. Functional disorders in the brain are associated with an abnormal hierarchical modular organization. The default mode network (DMN) is a complex dynamic network that is linked to specialized cognitive functions and clinically relevant information. In this study, we hypothesize that hierarchical functional segregation and integration of the DMN within attention-deficit/hyperactivity disorder (ADHD) is abnormal. We investigated topological metrics of both segregation and integration in different hierarchical subnetworks of the DMN between patients with ADHD and healthy controls. We found that the hierarchical functional integration and segregation of the DMN decreased and increased, respectively, in ADHD. Our results also indicated that the abnormalities in the DMN are intrinsically caused by changes in functional segregation and integration in its higher-level subnetworks. To better understand the temporally dynamic changes in the hierarchical functional integration and segregation of the DMN within ADHD, we further analyzed the dynamic transitions between functional segregation and integration. We found that the adaptive reorganizational ability of brain network states decreased in ADHD patients, which indicated less adaptive regulation between the DMN subnetworks in ADHD for supporting correspondingly normal cognitive function. From the perspective of hierarchical functional segregation and integration, our results further provide evidence to support dysfunctional brain cognitive functions within ADHD linked to brain network segregation and integration. [ABSTRACT FROM AUTHOR]

Many organisms, including the fathead minnow (Pimephales promelas), a toxicological model organism, establish social hierarchies. The social rank of each male in a population is under the control of the hypothalamic-pituitary-gonadal (HPG) axis mainly through regulation of circulating androgen concentrations, which in turn drive the expression of secondary sex characteristics (SSCs). As dominant and subordinate males in an exposure study are initially under different physiological conditions (i.e., differing plasma androgen concentrations), we proposed that they belong to different subpopulations in the context of exposure to compounds that may interact with the HPG axis. Using a meta-analysis of our data from several previously published studies, we corroborated the hypothesis that social status, as indicated by SSCs, results in distinct clusters (eigenvalues >0.8 explaining >80% of variability) with differential expression of plasma vitellogenin, a commonly used biomarker of exposure to contaminants of emerging concern (CEC). Furthermore, we confirmed our predictions that exposure to estrogenic CECs would homogenize plasma vitellogenin response (E1: cluster mean SSC values decreased to 4.33 and 4.86 relative to those of control; E2: decreased to 4.8 and 5.37) across the social hierarchy. In contrast, serotonin-specific reuptake inhibitors expand this response range (cluster mean SSC increased to 5.21 and 6.5 relative to those of control). Our results demonstrated that social hierarchies in male fathead minnows result in heterogeneous responses to chemical exposure. These results represent a cautionary note for the experimental design of single-sex exposure studies. We anticipate our study to be a starting point for the re-evaluation of toxicological data analyses in single sex exposure experiments. [ABSTRACT FROM AUTHOR]

In the current study, we evaluate the equivalent stiffness of peritubular reinforcement effect (PRE) of porous dentine optimized by the thickness of peritubular dentine (PTD). Few studies to date have evaluated or quantitated the effect of PRE on composite dentine. The miscrostructure of porous dentine is captured by scanning electron microscope images, and then finite element modeling is used to quantitate the deformation and stiffness of the porous dentine structure. By optimizing the radius of PTD and dentine tubule (DT), the proposed FE model is able to demonstrate the effect of peritubular reinforcement on porous dentine stiffness. It is concluded that the dentinal equivalent stiffness is reduced and degraded with the increase of the radius of DT (i.e., porosity) in the certain ratio value of Ep/Ei and certain radius of PTD, where Ep is the PTD modulus and Ei is the intertubular dentine modulus. So in order to ensure the whole dentinal equivalent stiffness is not loss, the porosity should get some value while the Ep/Ei is certain. Thus, PTD prevents the stress concentration around DTs and reduces the risk of DTs failure. Mechanically, the overall role of PTD appears to enhance the stiffness of the dentine composite structure. These results provide some new and significant insights into the biological evolution of the optimal design for the porous dentine microstructure. These findings on the biological microstructure design of dentine materials are applicable to other engineering structural designs aimed at increasing the overall structural strength. [ABSTRACT FROM AUTHOR]

Objective: Ibuprofen is used to prevent high altitude headache (HAH) but its efficacy remains controversial. We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials (RCTs) of ibuprofen for the prevention of HAH. Methods: Studies reporting efficacy of ibuprofen for prevention of HAH were identified by searching electronic databases (until December 2016). The primary outcome was the difference in incidence of HAH between ibuprofen and placebo groups. Risk ratios (RR) were aggregated using a Mantel-Haenszel random effect model. Heterogeneity of included trials was assessed using the I2 statistics. Results: In three randomized-controlled clinical trials involving 407 subjects, HAH occurred in 101 of 239 subjects (42%) who received ibuprofen and 96 of 168 (57%) who received placebo (RR = 0.79, 95% CI 0.66 to 0.96, Z = 2.43, P = 0.02, I2 = 0%). The absolute risk reduction (ARR) was 15%. Number needed to treat (NNT) to prevent HAH was 7. Similarly, The incidence of severe HAH was significant in the two groups (RR = 0.40, 95% CI 0.17 to 0.93, Z = 2.14, P = 0.03, I2 = 0%). Severe HAH occurred in 3% treated with ibuprofen and 10% with placebo. The ARR was 8%. NNT to prevent severe HAH was 13. Headache severity using a visual analogue scale was not different between ibuprofen and placebo. Similarly, the difference between the two groups in the change in SpO2 from baseline to altitude was not different. One included RCT reported one participant with black stools and three participants with stomach pain in the ibuprofen group, while seven participants reported stomach pain in the placebo group. Conclusions: Based on a limited number of studies ibuprofen seems efficacious for the prevention of HAH and may therefore represent an alternative for preventing HAH with acetazolamide or dexamethasone. [ABSTRACT FROM AUTHOR]