Topology of the lateral visual system: The fundus of the superior temporal sulcus and parietal area H connect nonvisual cerebrum to the lateral occipital lobe.

BACKGROUND AND PURPOSE: Mapping the topology of the visual system is critical for understanding how complex cognitive processes like reading can occur. We aim to describe the connectivity of the visual system to understand how the cerebrum accesses visual information in the lateral occipital lobe. METHODS: Using meta-analytic software focused on task-based functional MRI studies, an activation likelihood estimation (ALE) of the visual network was created. Regions of interest corresponding to the cortical parcellation scheme previously published under the Human Connectome Project were co-registered onto the ALE to identify the hub-like regions of the visual network. Diffusion Spectrum Imaging-based fiber tractography was performed to determine the structural connectivity of these regions with extraoccipital cortices. RESULTS: The fundus of the superior temporal sulcus (FST) and parietal area H (PH) were identified as hub-like regions for the visual network. FST and PH demonstrated several areas of coactivation beyond the occipital lobe and visual network. Furthermore, these parcellations were highly interconnected with other cortical regions throughout extraoccipital cortices related to their nonvisual functional roles. A cortical model demonstrating connections to these hub-like areas was created. CONCLUSIONS: FST and PH are two hub-like areas that demonstrate extensive functional coactivation and structural connections to nonvisual cerebrum. Their structural interconnectedness with language cortices along with the abnormal activation of areas commonly located in the temporo-occipital region in dyslexic individuals suggests possible important roles of FST and PH in the integration of information related to language and reading. Future studies should refine our model by examining the functional roles of these hub areas and their clinical significance.

An agile, data-driven approach for target selection in rTMS therapy for anxiety symptoms: Proof of concept and preliminary data for two novel targets.

INTRODUCTION: Data-driven approaches to transcranial magnetic stimulation (TMS) might yield more consistent and symptom-specific results based on individualized functional connectivity analyses compared to previous traditional approaches due to more precise targeting. We provide a proof of concept for an agile target selection paradigm based on using connectomic methods that can be used to detect patient-specific abnormal functional connectivity, guide treatment aimed at the most abnormal regions, and optimize the rapid development of new hypotheses for future study. METHODS: We used the resting-state functional MRI data of 28 patients with medically refractory generalized anxiety disorder to perform agile target selection based on abnormal functional connectivity patterns between the Default Mode Network (DMN) and Central Executive Network (CEN). The most abnormal areas of connectivity within these regions were selected for subsequent targeted TMS treatment by a machine learning based on an anomalous functional connectivity detection matrix. Areas with mostly hyperconnectivity were stimulated with continuous theta burst stimulation and the converse with intermittent theta burst stimulation. An image-guided accelerated theta burst stimulation paradigm was used for treatment. RESULTS: Areas 8Av and PGs demonstrated consistent abnormalities, particularly in the left hemisphere. Significant improvements were demonstrated in anxiety symptoms, and few, minor complications were reported (fatigue (n = 2) and headache (n = 1)). CONCLUSIONS: Our study suggests that a left-lateralized DMN is likely the primary functional network disturbed in anxiety-related disorders, which can be improved by identifying and targeting abnormal regions with a rapid, data-driven, agile aTBS treatment on an individualized basis.

Low- and High-Drag Intermittencies in Turbulent Channel Flows.

Recent direct numerical simulations (DNS) and experiments in turbulent channel flow have found intermittent low- and high-drag events in Newtonian fluid flows, at Reτ=uτh/ν between 70 and 100, where uτ, h and ν are the friction velocity, channel half-height and kinematic viscosity, respectively. These intervals of low-drag and high-drag have been termed "hibernating" and "hyperactive", respectively, and in this paper, a further investigation of these intermittent events is conducted using experimental and numerical techniques. For experiments, simultaneous measurements of wall shear stress and velocity are carried out in a channel flow facility using hot-film anemometry (HFA) and laser Doppler velocimetry (LDV), respectively, for Reτ between 70 and 250. For numerical simulations, DNS of a channel flow is performed in an extended domain at Reτ = 70 and 85. These intermittent events are selected by carrying out conditional sampling of the wall shear stress data based on a combined threshold magnitude and time-duration criteria. The use of three different scalings (so-called outer, inner and mixed) for the time-duration criterion for the conditional events is explored. It is found that if the time-duration criterion is kept constant in inner units, the frequency of occurrence of these conditional events remain insensitive to Reynolds number. There exists an exponential distribution of frequency of occurrence of the conditional events with respect to their duration, implying a potentially memoryless process. An explanation for the presence of a spike (or dip) in the ensemble-averaged wall shear stress data before and after the low-drag (or high-drag) events is investigated. During the low-drag events, the conditionally-averaged streamwise velocities get closer to Virk's maximum drag reduction (MDR) asymptote, near the wall, for all Reynolds numbers studied. Reynolds shear stress (RSS) characteristics during these conditional events are investigated for Reτ = 70 and 85. Except very close to the wall, the conditionally-averaged RSS is higher than the time-averaged value during the low-drag events.

Application of microfluidic devices for glioblastoma study: current status and future directions.

Glioblastoma (GBM) is one of the most malignant primary brain tumors. This neoplasm is the hardest to treat and has a bad prognosis. Because of the characteristics of genetic heterogeneity and frequent recurrence, a successful cure for the disease is unlikely. Increasing evidence has revealed that the GBM stem cell-like cells (GSCs) and microenvironment are key elements in GBM recurrence and treatment failure. To better understand the mechanisms underlying this disease and to develop more effective therapeutic strategies for treatment, suitable approaches, techniques, and model systems closely mimicking real GBM conditions are required. Microfluidic devices, a model system mimicking the in vivo brain microenvironment, provide a very useful tool to analyze GBM cell behavior, their correlation with tumor malignancy, and the efficacy of multiple drug treatment. This paper reviews the applications of microfluidic devices in GBM research and summarizes progress and perspectives in this field.

Engineering Biomimetic Nanofiber Microspheres with Tailored Size, Predesigned Structure, and Desired Composition via Gas Bubble-Mediated Coaxial Electrospray.

Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble-mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self-assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(ε-caprolactone), poly(lactic-co-glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto-responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.

Declines in skeletal muscle quality vs. size following two weeks of knee joint immobilization.

BACKGROUND: Disuse of a muscle group, which occurs during bedrest, spaceflight, and limb immobilization, results in atrophy. It is unclear, however, if the magnitude of decline in skeletal muscle quality is similar to that for muscle size. The purpose of this study was to examine the effects of two weeks of knee joint immobilization on vastus lateralis and rectus femoris echo intensity and cross-sectional area. METHODS: Thirteen females (mean ± SD age = 21 ± 2 years) underwent two weeks of left knee joint immobilization via ambulating on crutches and use of a brace. B-mode ultrasonography was utilized to obtain transverse plane images of the immobilized and control vastus lateralis and rectus femoris at pretest and following immobilization. Effect size statistics and two-way repeated measures analyses of variance were used to interpret the data. RESULTS: No meaningful changes were demonstrated for the control limb and the rectus femoris of the immobilized limb. Analyses showed a large increase in vastus lateralis echo intensity (i.e., decreased muscle quality) for the immobilized limb (p = .006, Cohen's d = .918). For vastus lateralis cross-sectional area, no time × limb interaction was observed (p = .103), but the effect size was moderate (d = .570). There was a significant association between the increase in vastus lateralis echo intensity and the decrease in cross-sectional area (r =  - .649, p = .016). CONCLUSION: In female participants, two weeks of knee joint immobilization resulted in greater deterioration of muscle quality than muscle size. Echo intensity appears to be an attractive clinical tool for monitoring muscle quality during disuse.

Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees.

Abnormal serum immunoglobulin (Ig) free light chains (FLC) are established biomarkers of early disease in multiple B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL). Heavy chains have also been shown to be biomarkers in plasma cell disorders. An unanswered question is whether these Ig biomarkers are heritable, i.e., influenced by germline factors. CLL is heritable but highly heterogeneous. Heritable biomarkers could elucidate steps of disease pathogenesis that are affected by germline factors, and may help partition heterogeneity and identify genetic pleiotropies across malignancies. Relatives in CLL pedigrees present an opportunity to identify heritable biomarkers. We compared FLCs and heavy chains between relatives in 23 high-risk CLL pedigrees and population controls. Elevated IgM (eIgM) and abnormal FLC (aFLC) ratio was significantly increased in relatives, suggesting that these Ig biomarkers are heritable and could offer risk stratification in pedigree relatives. Within high-risk CLL pedigrees, B-cell lymphoid malignancies were five times more prevalent in close relatives of individuals with eIgM, prostate cancer was three times more prevalent in relatives of individuals with aFLC, and monoclonal B-cell lymphocytosis increased surrounding individuals with normal Ig levels. These different clustering patterns suggest Ig biomarkers have the potential to partition genetic heterogeneity in CLL and provide insight into distinct heritable pleiotropies associated with CLL.

The role of the prostaglandin E2 receptors in vulnerability of oligodendrocyte precursor cells to death.

BACKGROUND: Activity of cyclooxygenase 2 (COX-2) in mouse oligodendrocyte precursor cells (OPCs) modulates vulnerability to excitotoxic challenge. The mechanism by which COX-2 renders OPCs more sensitive to excitotoxicity is not known. In the present study, we examined the hypothesis that OPC excitotoxic death is augmented by COX-2-generated prostaglandin E2 (PGE2) acting on specific prostanoid receptors which could contribute to OPC death. METHODS: Dispersed OPC cultures prepared from mice brains were examined for expression of PGE2 receptors and the ability to generate PGE2 following activation of glutamate receptors with kainic acid (KA). OPC death in cultures was induced by either KA, 3'-O-(Benzoyl) benzoyl ATP (BzATP) (which stimulates the purinergic receptor P2X7), or TNFα, and the effects of EP3 receptor agonists and antagonists on OPC viability were examined. RESULTS: Stimulation of OPC cultures with KA resulted in nearly a twofold increase in PGE2. OPCs expressed all four PGE receptors (EP1-EP4) as indicated by immunofluorescence and Western blot analyses; however, EP3 was the most abundantly expressed. The EP3 receptor was identified as a candidate contributing to OPC excitotoxic death based on pharmacological evidence. Treatment of OPCs with an EP1/EP3 agonist 17 phenyl-trinor PGE2 reversed protection from a COX-2 inhibitor while inhibition of EP3 receptor protected OPCs from excitotoxicity. Inhibition with an EP1 antagonist had no effect on OPC excitotoxic death. Moreover, inhibition of EP3 was protective against toxic stimulation with KA, BzATP, or TNFα. CONCLUSION: Therefore, inhibitors of the EP3 receptor appear to enhance survival of OPCs following toxic challenge and may help facilitate remyelination.

The impact of roadway intersection design on driving performance of young and senior adults.

OBJECTIVE: To test the effectiveness of the FHWA guidelines for intersection design. METHODS: In an experimental design we used kinematics measures from an instrumented vehicle and behavioral (error) data collected during on-road evaluations to quantify the effects of improved versus unimproved intersections (turn phase) and to determine if these intersections were safer (vehicular stability and driver confidence) for both older (65-85 years) and younger (25 -45) drivers. We analyzed kinematics data with a 2 x 2 repeated measures ANOVA and behavioral data (driving errors yes, no) with Wilcoxon sign rank test (within subject variable: intersection improved vs. unimproved) and Wilcoxon rank sum test (between subject variable: age, younger vs. older driver). RESULTS: Kinematics measures (turn phase), showed three maneuvers had statistically significantly lesser side forces (measured by lateral acceleration and combined acceleration) for the improved conditions, and four maneuvers had statistically significantly greater, yet appropriate, speeds for the improved conditions. Lesser side forces indicated improved lateral stability and increased speed indicated greater confidence. Drivers made fewer errors on two of the improved intersections; but across all maneuvers, older drivers appeared to make fewer errors on the improved intersections. CONCLUSIONS: This study brings empirical intersection design and safety information for engineers and city planners to consider as they plan and develop intersections. Future researchers may want to use the conceptual and analytical framework of this study to determine the effectiveness of other FHWA guidelines. Given that these intersection design guidelines benefit younger and older drivers alike, plausible policy-making opportunities are opened in the design of safe roadway systems, to benefit the broad spectrum of adult drivers.

The impact of intersection design on simulated driving performance of young and senior adults.

PURPOSE: The Federal Highway Administration (FHWA) proposed guidelines for highway design to increase the safe driving ability of older drivers; however, little empirical evidence exists to support the effectiveness of these guidelines. The purpose of this study was to investigate the effects of implementing these guidelines (in 4 pairs of intersections) on safe driving performance of older and younger drivers using a high-fidelity driving simulator. DESIGN AND METHODS: We replicated four intersection pairs (improved versus unimproved) in a high-fidelity, virtual reality driving simulator. Simulator scenarios were created from actual road locations, replicating road geometrics and traffic control devices. The simulator's controls were integrated with an actual vehicle to make the driving experience as realistic as possible. Kinematic measures were obtained from the simulator in conjunction with driving errors recorded by trained driving evaluators sitting in the cab of the car. Thirty-nine subjects, 19 younger and 20 older adults, participated in the study. RESULTS: For the kinematic data we found greater lateral control, as indicated by significantly smaller maximum yaw during the turn phase, at all of the improved intersections when compared to the unimproved intersections. We found some significant age differences, but mostly in only one of the intersection-pairs. For the behavioral data, there were significant differences in driving errors between improved and unimproved intersections in two intersection-pairs; however, there were no significant differences in driving errors between the older and younger drivers. IMPLICATIONS: The findings suggest that both young and older drivers may benefit from roadways with safety features recommended by the FHWA guidelines as indicated by the increased lateral control of the vehicle when negotiating these intersections. These findings generate critical information for those involved in the design of roadway systems.