Genetic Approaches to Hypothalamic-Pituitary-Adrenal Axis Regulation

The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with pathologic, psychological, and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, among others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models have allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation.     

Extended Kalman smoother with differential evolution technique for denoising of ECG signal

Electrocardiogram (ECG) signal gives a lot of information on the physiology of heart. In reality, noise from various sources interfere with the ECG signal. To get the correct information on physiology of the heart, noise cancellation of the ECG signal is required. In this paper, the effectiveness of extended Kalman smoother (EKS) with the differential evolution (DE) technique for noise cancellation of the ECG signal is investigated. DE is used as an automatic parameter selection method for the selection of ten optimized components of the ECG signal, and those are used to create the ECG signal according to the real ECG signal. These parameters are used by the EKS for the development of the state equation and also for initialization of the parameters of EKS. EKS framework is used for denoising the ECG signal from the single channel. The effectiveness of proposed noise cancellation technique has been evaluated by adding white, colored Gaussian noise and real muscle artifact noise at different SNR to some visually clean ECG signals from the MIT-BIH arrhythmia database. The proposed noise cancellation technique of ECG signal shows better signal to noise ratio (SNR) improvement, lesser mean square error (MSE) and percent of distortion (PRD) compared to other well-known methods.     

The Importance of Venous Return in Starling‐Like Control of Rotary Ventricular Assist Devices

Rotary ventricular assist devices (VADs) are less sensitive to preload than the healthy heart, resulting in inadequate flow regulation in response to changes in patient cardiac demand. Starling‐like physiological controllers (SLCs) have been developed to automatically regulate VAD flow based on ventricular preload. An SLC consists of a cardiac response curve (CRC) which imposes a nonlinear relationship between VAD flow and ventricular preload, and a venous return line (VRL) which determines the return path of the controller. This study investigates the importance of a physiological VRL in SLC of dual rotary blood pumps for biventricular support. Two experiments were conducted on a physical mock circulation loop (MCL); the first compared an SLC with an angled physiological VRL (SLC‐P) against an SLC with a vertical VRL (SLC‐V). The second experiment quantified the benefit of a dynamic VRL, represented by a series of specific VRLs, which could adapt to different circulatory states including changes in pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed physiological VRL which was calculated at rest. In both sets of experiments, the transient controller responses were evaluated through reductions in preload caused by the removal of fluid from the MCL. The SLC‐P produced no overshoot or oscillations following step changes in preload, whereas SLC‐V produced 0.4 L/min (12.5%) overshoot for both left and right VADs. Additionally, the SLC‐V had increased settling time and reduced controller stability as evidenced by transient controller oscillations. The transient results comparing the specific and standard VRLs demonstrated that specific VRL rise times were improved by between 1.2 and 4.7 s ( = 3.05 s), while specific VRL settling times were improved by between 2.8 and 16.1 seconds ( = 8.38 s) over the standard VRL. This suggests only a minor improvement in controller response time from a dynamic VRL compared to the fixed VRL. These results indicate that the use of a fixed physiologically representative VRL is adequate over a wide variety of physiological conditions.