Multimodal Assessment of the Pulse Rate Variability Analysis Module of a Photoplethysmography-Based Telemedicine System

Alterations of heart rate variability (HRV) are associated with various (patho)physiological conditions; therefore, HRV analysis has the potential to become a useful diagnostic module of wearable/telemedical devices to support remote cardiovascular/autonomic monitoring. Continuous pulse recordings obtained by photoplethysmography (PPG) can yield pulse rate variability (PRV) indices similar to HRV parameters; however, it is debated whether PRV/HRV parameters are interchangeable. In this study, we assessed the PRV analysis module of a digital arterial PPG-based telemedical system (SCN4ALL). We used Bland–Altman analysis to validate the SCN4ALL PRV algorithm to Kubios Premium software and to determine the agreements between PRV/HRV results calculated from 2-min long PPG and ECG captures recorded simultaneously in healthy individuals (n = 33) at rest and during the cold pressor test, and in diabetic patients (n = 12) at rest. We found an ideal agreement between SCN4ALL and Kubios outputs (bias < 2%). PRV and HRV parameters showed good agreements for interbeat intervals, SDNN, and RMSSD time-domain variables, for total spectral and low-frequency power (LF) frequency-domain variables, and for non-linear parameters in healthy subjects at rest and during cold pressor challenge. In diabetics, good agreements were observed for SDNN, LF, and SD2; and moderate agreement was observed for total power. In conclusion, the SCN4ALL PRV analysis module is a good alternative for HRV analysis for numerous conventional HRV parameters

Selective Fluorescent Probes for High-Throughput Functional Diagnostics of the Human Multidrug Transporter P-Glycoprotein (ABCB1)

The multidrug transporter ABCB1 (MDR1, Pgp) plays an important role in the absorption, distribution, metabolism, and elimination of a wide range of pharmaceutical compounds. Functional investigation of the ABCB1 expression is also essential in many diseases, including drug-resistant cancer, inflammatory conditions, or Alzheimer disease. In this study, we examined the potential interaction of the ABCB1 multidrug transporter with a group of commercially available viability dyes that are generally considered not to penetrate into intact cells. Here, we demonstrate that the slow cellular accumulation of TO-PRO™-1 (TP1) or TO-PRO™-3 (TP3) was strongly inhibited by ABCB1-dependent dye extrusion. TP1/3 dye accumulation was not affected by the presence of ABCC1 or ABCG2, while this uptake was increased to the level in the ABCB1-negative cells by a specific P-glycoprotein inhibitor, Tariquidar. We suggest that TP compounds can be used as highly sensitive, selective, non-toxic, and stable dyes to examine the functional expression and properties of the ABCB1 multidrug transporter, especially in microplate-based high-throughput flow cytometry assays. In addition, we demonstrate the applicability of the TP dyes to efficiently select and separate even a very low number of Pgp-expressing intact cells

Genetic Modulation of the GLUT1 Transporter Expression—Potential Relevance in Complex Diseases

The human GLUT1 (SLC2A1) membrane protein is the key glucose transporter in numerous cell types, including red cells, kidney, and blood-brain barrier cells. The expression level of this protein has a role in several diseases, including cancer and Alzheimer’s disease. In this work, to investigate a potential genetic modulation of the GLUT1 expression level, the protein level was measured in red cell membranes by flow cytometry, and the genetic background was analyzed by qPCR and luciferase assays. We found significant associations between red cell GLUT1 levels and four single nucleotide polymorphisms (SNP) in the coding SLC2A1 gene, that in individuals with the minor alleles of rs841848, rs1385129, and rs11537641 had increased, while those having the variant rs841847 had decreased erythrocyte GLUT1 levels. In the luciferase reporter studies performed in HEK-293T and HepG2 cells, a similar SNP-dependent modulation was observed, and lower glucose, serum, and hypoxic condition had variable, cell- and SNP-specific effects on luciferase expression. These results should contribute to a more detailed understanding of the genetic background of membrane GLUT1 expression and its potential role in associated diseases