Disrupted functional brain network organization in patients with obstructive sleep apnea.

IntroductionObstructive sleep apnea (OSA) subjects show impaired autonomic, affective, executive, sensorimotor, and cognitive functions. Brain injury in OSA subjects appears in multiple sites regulating these functions, but the integrity of functional networks within the regulatory sites remains unclear. Our aim was to examine the functional interactions and the complex network organization of these interactions across the whole brain in OSA, using regional functional connectivity (FC) and brain network topological properties.MethodsWe collected resting-state functional magnetic resonance imaging (MRI) data, using a 3.0-Tesla MRI scanner, from 69 newly diagnosed, treatment-naïve, moderate-to-severe OSA (age, 48.3 ± 9.2 years; body mass index, 31 ± 6.2 kg/m(2); apnea-hypopnea index (AHI), 35.6 ± 23.3 events/h) and 82 control subjects (47.6 ± 9.1 years; body mass index, 25.1 ± 3.5 kg/m(2)). Data were analyzed to examine FC in OSA over controls as interregional correlations and brain network topological properties.ResultsObstructive sleep apnea subjects showed significantly altered FC in the cerebellar, frontal, parietal, temporal, occipital, limbic, and basal ganglia regions (FDR, P < 0.05). Entire functional brain networks in OSA subjects showed significantly less efficient integration, and their regional topological properties of functional integration and specialization characteristics also showed declined trends in areas showing altered FC, an outcome which would interfere with brain network organization (P < 0.05; 10,000 permutations). Brain sites with abnormal topological properties in OSA showed significant relationships with AHI scores.ConclusionsOur findings suggest that the dysfunction extends to resting conditions, and the altered FC and impaired network organization may underlie the impaired responses in autonomic, cognitive, and sensorimotor functions. The outcomes likely result from the prominent structural changes in both axons and nuclear structures, which occur in the condition

Intracellular Nanomaterial Delivery via Spiral Hydroporation

In recent nanobiotechnology developments, a wide variety of functional nanomaterials and engineered biomolecules have been created, and these have numerous applications in cell biology. For these nanomaterials to fulfill their promises completely, they must be able to reach their biological targets at the subcellular level and with a high level of specificity. Traditionally, either nanocarrier- or membrane disruption-based method has been used to deliver nanomaterials inside cells; however, these methods are suboptimal due to their toxicity, inconsistent delivery, and low throughput, and they are also labor intensive and time-consuming, highlighting the need for development of a next-generation, intracellular delivery system. This study reports on the development of an intracellular nanomaterial delivery platform, based on unexpected cell-deformation phenomena via spiral vortex and vortex breakdown exerted in the cross- and T-junctions at moderate Reynolds numbers. These vortex-induced cell deformation and sequential restoration processes open cell membranes transiently, allowing effective and robust intracellular delivery of nanomaterials in a single step without the aid of carriers or external apparatus. By using the platform described here (termed spiral hydroporator), we demonstrate the delivery of different nanomaterials, including gold nanoparticles (200 nm diameter), functional mesoporous silica nanoparticles (150 nm diameter), dextran (hydrodynamic diameters between 2–55 nm), and mRNA, into different cell types. We demonstrate here that the system is highly efficient (up to 96.5%) with high throughput (up to 1 × 106 cells/min) and rapid delivery (∼1 min) while maintaining high levels of cell viability (up to 94%)

Critical flux pinning and enhanced upper-critical-field in magnesium diboride films

We have conducted pulsed transport measurements on c-axis oriented magnesium diboride films over the entire relevant ranges of magnetic field 0 \alt H \alt H_{c2} (where \hcu is the upper critical field) and current density 0 \alt j \alt j_{d} (where $j_{d}$ is the depairing current density). The intrinsic disorder of the films combined with the large coherence length and three-dimensionality, compared to cuprate superconductors, results in a six-fold enhancement of $H_{c2}$ and raises the depinning current density $j_{c}$ to within an order of magnitude of $j_{d}$. The current-voltage response is highly non-linear at all fields, resulting from a combination of depinning and pair-breaking, and has no trace of an Ohmic free-flux-flow regime. Keywords: pair, breaking, depairing, superconductor, superconductivity, flux, fluxon, vortex, mgb

Two-Species Annihilation with Drift: A Model with Continuous Concentration-Decay Exponents

We propose a model for diffusion-limited annihilation of two species, $A+B\to A$ or $B$, where the motion of the particles is subject to a drift. For equal initial concentrations of the two species, the density follows a power-law decay for large times. However, the decay exponent varies continuously as a function of the probability of which particle, the hopping one or the target, survives in the reaction. These results suggest that diffusion-limited reactions subject to drift do not fall into a limited number of universality classes.Comment: 10 pages, tex, 3 figures, also available upon reques

Prognostic relevance of symptoms versus objective evidence of coronary artery disease in diabetic patients

Aim Little is known about the prognostic significance of silent versus symptomatic coronary artery disease (CAD) in diabetic patients. We therefore assessed the incidence of scintigraphic evidence of CAD in diabetic patients without known CAD and the impact of symptoms and scintigraphic findings on prognosis. Methods and results A consecutive series of 1737 diabetic patients without known CAD underwent dual-isotope myocardial perfusion SPECT (MPS) and 1430 were followed-up for a median of 2 (1-8.5) years. Critical events were defined as myocardial infarction or cardiac death. Objective evidence of CAD was found in 39% of 826 asymptomatic diabetic patients, in 51% of 151 diabetic patients with shortness of breath (SOB), and in 44% of 760 diabetic patients with angina. During follow-up, 98 critical events occurred. Annual critical event rates were 2.2% in asymptomatic, 3.2% in angina, and 7.7% in diabetic patients with shortness of breath (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $p{<}0.001$ \end{document} versus other groups). With MPS evidence of CAD, critical event rates increased to 3.4% (asymptomatic), 5.6% (angina), and 13.2% (SOB) (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $p{\leqslant}0.009$ \end{document} versus no evidence of CAD). Age, hypertension, shortness of breath, scarring and ischaemia were independent predictors of critical events. MPS findings added incremental information to prescan information regarding outcome prediction. Conclusions In asymptomatic diabetic patients, the rate of objective evidence of CAD and annual critical events were similar to those found in diabetic patients with angina. The outcome was three times worse in diabetic patients with shortness of breath. MPS findings were strongly predictive of outcome and proved valuable for risk stratificatio

Enhanced mitochondrial superoxide scavenging does not Improve muscle insulin action in the high fat-fed mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging

Complete Exact Solution of Diffusion-Limited Coalescence, A + A -> A

Some models of diffusion-limited reaction processes in one dimension lend themselves to exact analysis. The known approaches yield exact expressions for a limited number of quantities of interest, such as the particle concentration, or the distribution of distances between nearest particles. However, a full characterization of a particle system is only provided by the infinite hierarchy of multiple-point density correlation functions. We derive an exact description of the full hierarchy of correlation functions for the diffusion-limited irreversible coalescence process A + A -> A.Comment: 4 pages, 2 figures (postscript). Typeset with Revte

Model-Based Reconstructive Elasticity Imaging Using Ultrasound

Elasticity imaging is a reconstructive imaging technique where tissue motion in response to mechanical excitation is measured using modern imaging systems, and the estimated displacements are then used to reconstruct the spatial distribution of Young's modulus. Here we present an ultrasound elasticity imaging method that utilizes the model-based technique for Young's modulus reconstruction. Based on the geometry of the imaged object, only one axial component of the strain tensor is used. The numerical implementation of the method is highly efficient because the reconstruction is based on an analytic solution of the forward elastic problem. The model-based approach is illustrated using two potential clinical applications: differentiation of liver hemangioma and staging of deep venous thrombosis. Overall, these studies demonstrate that model-based reconstructive elasticity imaging can be used in applications where the geometry of the object and the surrounding tissue is somewhat known and certain assumptions about the pathology can be made