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Summary: Autosomal-dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by the formation of fluid-filled renal cysts, loss of mitochondrial function, decreased fatty acid oxidation, increased glycolysis, and likely renal failure. We previously demonstrated that inducing a state of ketosis ameliorates or reverses PKD progression in multiple animal models. In this study, we compare time-restricted feeding and 48-h periodic fasting regimens in both juvenile and adult Cy/+ rats. Both fasting regimens potently prevent juvenile disease progression and partially reverse PKD in adults. To explore the mechanism of fasting, we administered β-hydroxybutyrate (BHB) to Cy/+ rats and orthologous mouse models of PKD (Pkd1RC/RC, Pkd1-Ksp:Cre). BHB recapitulated the effects of fasting in these models independent of stereoisomer, suggesting the effects of BHB are largely due to its signaling functions. These findings implicate the use of ketogenic metabolic therapy and BHB supplementation as potential disease modifiers of PKD and point toward underlying mechanisms.

Introduction: Prehypertension is the precursor to high Blood Pressure (BP), which can lead to severe consequences such as cardiovascular disease, stroke, acute myocardial infarction, heart failure, peripheral arterial disease, and cerebrovascular complications, ultimately resulting in mortality. Vagal stimulation is frequently employed by therapists, along with various therapeutic exercises, to treat or manage Heart Rate (HR) and BP in prehypertensive individuals. The vagus nerve plays a vital role in maintaining internal physiological balance, known as homeostasis, which includes reflex pathways that regulate cardiac function. Auricular neuromodulation of the vagus nerve can be achieved through stimulation of the ear lobule, cymba concha, or tragus in the outer ear. Aim: To compare and determine the optimal anatomical site for vagal stimulation, specifically the ear lobule, cymba concha, or tragus, to improve HR, BP, and skin hydration in prehypertensive individuals. Materials and Methods: The present pilot study conducted a pre-post comparative analysis in the Outpatient Department (OPD) of Physiotherapy at the Institute of Applied Medicines and Research Centre, Ghaziabad, Uttar Pradesh, India. The study duration was nine months, from January 2022 to September 2022. A total of 30 subjects aged 30-55 years were divided into three groups (10 participants in each group: A, B, and C) using sealed envelopes. Group A received vagal stimulation on the ear lobule, Group B received vagal stimulation on the cymba concha, and Group C received vagal stimulation on the tragus. Baseline measurements were taken prior to treatment, including HR, BP, and skin hydration. Vagal stimulation was administered using a low-frequency Transcutaneous Electrical Nerve Stimulation (TENS) machine at 25 Hertz and a pulse width of 120 ms. The stimulus was continuously applied for 30 minutes, five days a week, for four weeks. After a 10-minute relaxation period, HR, BP, and skin hydration were measured both pre and post-intervention. The data was statistically analysed using Statistical Package for Social Sciences (SPSS) version 24.0, employing paired t-tests to compare means within groups and Analysis of Variance (ANOVA) to compare between the three groups. Results: There were no statistical differences in the baseline among all three groups. Group C, which received vagal stimulation on the tragus, demonstrated statistically significant improvements in BP and skin hydration. The t-value and p-value for Systolic Blood Pressure (SBP) were 11.513 and p