Kv1.1 deficiency alters repetitive and social behaviors in mice and rescues autistic-like behaviors due to Scn2a haploinsufficiency.

Background: Autism spectrum disorder (ASD) and epilepsy are highly comorbid, suggesting potential overlap in genetic etiology, pathophysiology, and neurodevelopmental abnormalities; however, the nature of this relationship remains unclear. This work investigated how two ion channel mutations, one associated with autism (Scn2a-null) and one with epilepsy (Kcna1-null), interact to modify genotype-phenotype relationships in the context of autism. Previous studies have shown that Scn2a ameliorates epilepsy in Kcna1 mice, improving survival, seizure characteristics, and brain-heart dynamics.

Directed Connectivity Analysis of the Neuro-Cardio- and Respiratory Systems Reveals Novel Biomarkers of Susceptibility to SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality and its pathophysiological mechanisms remain unknown. We set to record and analyze for the first time concurrent electroencephalographic (EEG), electrocardiographic (ECG), and unrestrained whole-body plethysmographic (Pleth) signals from control (WT - wild type) and SUDEP-prone mice (KO- knockout Kcna1 animal model). Employing multivariate autoregressive models (MVAR) we measured all tri-organ effective directional interactions by the generalized partial directed coherence (GPDC) in the frequency domain over time (hours).

Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity.

Background & Objectives: Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals.

Methods: Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015.

Endothelial nitric oxide synthase gene polymorphisms are associated with cardiovascular risks in prehypertensives.

Though endothelial nitric oxide synthase (eNOS) gene polymorphism is documented in the causation of hypertension, its role in prehypertension has not been investigated. The present study was conducted in 172 subjects divided into prehypertensives (n = 57) and normotensives (n = 115). Cardiovascular (CV) parameters including baroreflex sensitivity (BRS) by continuous BP variability assessment and sympathovagal imbalance (SVI) by heart rate variability analysis were recorded.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, body fat mass and altered cardiometabolic profile in pre-obesity and obesity.

Objective: Though decreased baroreflex sensitivity (BRS), the predictor of cardiac morbidities and mortality has been reported in obesity, the mechanisms and metabolic biomarkers influencing BRS have not been studied. We aimed to assess the difference in cardiovascular (CV) risk profile in pre-obesity and obesity, and the contribution of body composition and cardiometabolic factors to CV risks in these two conditions.

Methods: Obesity indices, body composition, blood pressure variability and autonomic function test parameters were recorded in 223 subjects divided into controls (n=72), pre-obese (n=77) and obese (n=74) groups.

Prehypertension status, cardiometabolic risks, and decreased baroreflex sensitivity are linked to sympathovagal imbalance in salt-preferring individuals.

Salt preference has been reported to cause sympathovagal imbalance (SVI) and prehypertension. We investigated the role of inflammation, insulin resistance (IR), hyperlipidemia, and oxidative stress (OS) in genesis of SVI and cardiovascular (CV) risks in salt-preferring prehypertensives. The subjects were divided into no-salt-preferring (NSP, n = 87) and salt-preferring (SP, n = 89) group based on their preference for salted food.

Association of sympathovagal imbalance with obesity indices, and abnormal metabolic biomarkers and cardiovascular parameters.

Problem: Pathophysiological mechanisms contributing to abnormal cardiovascular (CV) parameters in obesity have not been fully elucidated. Role of sympathovagal imbalance (SVI) in the prediction of abnormalities in CV functions in obesity has not been studied.

Methods: Anthropometric indices, CV parameters, autonomic function tests (AFTs) such as spectral heart rate variability (HRV) analysis, heart rate and blood pressure response to standing, deep breathing, and isometric-handgrip, and biochemical parameters like insulin resistance (HOMA-IR), lipid risk factors and inflammatory marker [high-sensitive C-reactive protein (hsCRP)] were assessed in control group (non-obese, n=43) and obese group (n=45).