Aligned electrospun fibers for neural patterning

OBJECTIVES: To test a 3D approach for neural network formation, alignment, and patterning that is reproducible and sufficiently stable to allow for easy manipulation. RESULTS: A novel cell culture system was designed by engineering a method for the directional growth of neurons. This uses NG108-15 neuroblastoma x glioma hybrid cells cultured on suspended and aligned electrospun fibers. These fiber networks improved cellular directionality, with alignment angle standard deviations significantly lower on fibers than on regular culture surfaces. Morphological studies found nuclear aspect ratios and cell projection lengths to be unchanged, indicating that cells maintained neural morphology while growing on fibers and forming a 3D network. Furthermore, fibronectin-coated fibers enhanced neurite extensions for all investigated time points. Differentiated neurons exhibited significant increases in average neurite lengths 96 h post plating, and formed neurite extensions parallel to suspended fibers, as visualized through scanning electron microscopy. CONCLUSIONS: The developed model has the potential to serve as the basis for advanced 3D studies, providing an original approach to neural network patterning and setting the groundwork for further investigations into functionality

Insulin resistance and reduced cardiac autonomic function in older adults: the Atherosclerosis Risk in Communities study

Background: Prior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities. Methods: We examined older adults without diabetes with 48-h ambulatory electrocardiography (n = 759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was defined by quartiles for three indexes: 1) the homeostatic model assessment of insulin resistance (HOMA-IR), 2) the triglyceride and glucose index (TyG), and 3) the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Low heart rate variability, the outcome, was defined by <25th percentile for four measures: 1) standard deviation of normal-to-normal R-R intervals (SDNN), a measure of total variability; 2) root mean square of successive differences in normal-to-normal R-R intervals (RMSSD), a measure of vagal activity; 3) low frequency spectral component (LF), a measure of sympathetic and vagal activity; and 4) high frequency spectral component (HF), a measure of vagal activity. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals weighted for sampling/non-response, adjusted for age at ancillary visit, sex, and race/study-site. Insulin resistance quartiles 4, 3, and 2 were compared to quartile 1; high indexes refer to quartile 4 versus quartile 1. Results: The average age was 78 years, 66% (n = 497) were women, and 58% (n = 438) were African American. Estimates of association were not robust at all levels of HOMA-IR, TyG, and TG/HDL-C, but suggest that high indexes were associated consistently with indicators of vagal activity. High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low RMSSD (OR: 1.68 (1.00, 2.81), OR: 2.03 (1.21, 3.39), and OR: 1.73 (1.01, 2.91), respectively). High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low HF (OR: 1.90 (1.14, 3.18), OR: 1.98 (1.21, 3.25), and OR: 1.76 (1.07, 2.90), respectively). Conclusions: In older adults without diabetes, insulin resistance was associated with reduced cardiac autonomic function - specifically and consistently for indicators of vagal activity - measured during daily activities. Primary prevention of insulin resistance may reduce the related risk of cardiac autonomic dysfunction

Interferon gamma: is it a co-player in the pathogenesis of idiopathic nephrotic syndrome

Introduction: Idiopathic nephrotic syndrome (INS), the most common form of NS in childhood, was considered 4 decades ago as a systemic disorder of T cells, mediated through its released cytokines. To date, the exact incriminated cytokine or immunological mediator is not properly defined. Interferon gamma (IFN-γ), a pro-inflammatory cytokine, is thought to have a role in the provocation of the T cell mediated INS relapse, through promotion of T helper1 (Th1) differentiation and suppression of regulatory T cells (Treg). Aim of the study: to evaluate the immunopathogenic role of IFN-γ in children with steroid sensitive idiopathic nephrotic syndrome (SSNS) through monitoring the changes in its levels with disease course. Methods: This study included twenty-five newly diagnosed children with SSINS. They were all given full dose prednisolone, evaluated at initial diagnosis and at full remission as regards the serum level of IFN-γ. Results: Serum levels of IFN-γ were lowermost at time of diagnosis and increased with remission on corticosteroids. Conclusions: this study points to a role for the lower serum IFN-γ at diagnosis, in the immunopathogenesis of INS than at remission and the rise in its serum level might be a marker of remission induction, however this awaits confirmation in larger scale studies. Studies on renal biopsy specimens are needed to determine the exact renal in situ levels and effects of IFN-

Long-term prognosis associated with J-point elevation in a large middle-aged biracial cohort: the ARIC study

An association has been described between death from arrhythmia and early repolarization, an electrocardiogram pattern characterized by elevation of the QRS–ST junction (J-point). Little is known about this relationship in non-white populations. This study examines the relationship between J-point elevation (JPE) and sudden cardiac death (SCD) and whether this relationship differs by race or sex

Symbolic analysis of analog circuits containing voltage mirrors

7 páginas, 7 figuras, 2 tablas, 4 imágenes.-- Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License.The pathological elements voltage mirror (VM) and current mirror (CM) have shown advantages in analog behavioral modeling and circuit synthesis, where many nullor-mirror equivalences have been explored to design and to transform voltage-mode circuits to current-mode ones and viceversa. However, both the VM and CM have not equivalents to perform automatic symbolic circuit analysis. In this manner, we introduce nullor-equivalents for these pathological elements allowing to include parasitics and to perform only symbolic nodal analysis. The nullor-equivalent of the CM is extended to provide multiple-outpus (MO-CM). Finally, two active filters containing VMs, CMs and MO-CMs are analysed to show the usefulness of the models.This work is supported by: UC-MEXUS and CONACyT under grants CN-09-310 and 48396-Y; by Promep-Mexico under grant UATLX-PTC-088; by Consejeria de Innovacion, Ciencia y Empresa, Junta de Andalucia-Spain TIC-2532; and by the JAE-Doc program of CSIC co-funded by FSE, Spain.Peer reviewe

Electrocardiographic Predictors of Coronary Heart Disease and Sudden Cardiac Deaths in Men and Women Free From Cardiovascular Disease in the Atherosclerosis Risk in Communities Study

BackgroundWe evaluated predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) study.Methods and ResultsThe study population included 13 621 men and women 45 to 65 years of age free from manifest cardiovascular disease at entry. Hazard ratios from Cox regression with 95% confidence intervals were computed for 18 dichotomized repolarization‐related ECG variables. The average follow‐up was 14 years. Independent predictors of CHD death in men were TaVR‐ and rate‐adjusted QTend (QTea), with a 2‐fold increased risk for both, and spatial angles between mean QRS and T vectors and between Tpeak (Tp) and normal R reference vectors [θ(Rm|Tm) and θ(Tp|Tref), respectively], with a >1.5‐fold increased risk for both. In women, independent predictors of the risk of CHD death were θ(Rm|Tm), with a 2‐fold increased risk for θ(Rm|Tm), and θ(Tp|Tref), with a 1.7‐fold increased risk. Independent predictors of SCD in men were θ(Tp|Tref) and QTea, with a 2‐fold increased risk, and θ(Tinit|Tterm), with a 1.6‐fold increased risk. In women, θ(Tinit|Tterm) was an independent predictor of SCD, with a >3‐fold increased risk, and θ(Rm|Tm) and TV1 were >2‐fold for both.Conclusionsθ(Rm|Tm) and θ(Tp|Tref), reflecting different aspects of ventricular repolarization, were independent predictors of CHD death and SCD, and TaVR and TV1 were also independent predictors. The risk levels for independent predictors for both CHD death and SCD were stronger in women than in men, and QTea was a significant predictor in men but not in women

Socioeconomic Status and the Incidence of Atrial Fibrillation in Whites and Blacks: The Atherosclerosis Risk in Communities (ARIC) Study

BackgroundNo previous studies have examined the interplay among socioeconomic status, sex, and race with the risk of atrial fibrillation (AF).Methods and ResultsWe prospectively followed 14 352 persons (25% black, 75% white, 55% women, mean age 54 years) who were free of AF and participating in the Atherosclerosis Risk in Communities (ARIC) study. Socioeconomic status was assessed at baseline (1987–1989) through educational level and total family income. Incident AF through 2009 was ascertained from electrocardiograms, hospitalizations, and death certificates. Cox regression was used to estimate hazard ratios and 95% CIs of AF for education and family income. Interactions were tested between socioeconomic status and age, race, or sex. Over a median follow‐up of 20.6 years, 1794 AF cases occurred. Lower family income was associated with higher AF risk (hazard ratio 1.45, 95% CI 1.27 to 1.67 in those with income less than $25 000 per year compared with those with$50 000 or more per year). The association between education and AF risk varied by sex (P=0.01), with the lowest education group associated with higher AF risk in women (hazard ratio 1.88, 95% CI 1.55 to 2.28) but not in men (hazard ratio 1.15, 95% CI 0.97 to 1.36) compared with the highest education group. Adjustment for cardiovascular risk factors attenuated the associations. There were no interactions with race or age. Blacks had lower AF risk than whites in all income and education groups.ConclusionsLower family income was associated with a higher AF risk overall, whereas the impact of education on AF risk was present only in women. Differences in socioeconomic status do not explain the lower risk of AF in blacks compared with whites

Smoking and incidence of atrial fibrillation: Results from the Atherosclerosis Risk in Communities (ARIC) Study

Cigarette smoking increases the risk of coronary heart disease, but whether smoking increases atrial fibrillation (AF) is uncertain

A Clinical Risk Score for Atrial Fibrillation in a Biracial Prospective Cohort (from the Atherosclerosis Risk In Communities [ARIC] Study)

A risk score for AF has been developed by the Framingham Heart Study; however the applicability of this risk score, derived from whites, to predict new-onset AF in non-whites is uncertain. Therefore, we developed a 10-year risk score for new-onset AF using risk factors commonly measured in clinical practice using 14,546 individuals from the Atherosclerosis Risk in Communities study, a prospective community-based cohort of blacks and whites in the United States. During 10 years of follow-up, 515 incident AF events occurred. The following variables were included in the AF risk score: age, race, height, smoking status, systolic blood pressure, hypertension medication usage, precordial murmur, left ventricular hypertrophy, left atrial enlargement, diabetes, coronary heart disease, and heart failure. The area under the receiver-operating characteristics curve (AUC) of a Cox regression model including the previous variables was 0.78, suggesting moderately good discrimination. The point-based score developed from coefficients in the Cox model had an AUC of 0.76. This clinical risk score for AF in the ARIC cohort compared favorably with the Framingham Heart Study’s AF (AUC=0.68), CHD (AUC=0.63), and hard CHD (AUC=0.59) risk scores and the ARIC CHD risk score (AUC=0.58). In conclusion, we have developed a risk score for AF and have shown that the different pathophysiologies of AF and CHD limit the usefulness of a CHD risk score at identifying individuals at higher risk of AF