Real-time Monitoring Excitation Dynamics of Human Telomeric Guanine Quadruplexes: Effect of Folding Topology, Metal Cation, and Confinement by Nanocavity Water Pool.

Guanine(G)-rich human telomeric (HT) DNA repeats, crucial to maintenance of genome stability, readily form G-quadruplexes (GQs) with various folding topologies. Research on excitation dynamics of HT-GQs is, however, scarce. Herein, we report a femtosecond time-resolved fluorescence coupled with transient absorption investigation on HT-GQ with the basket-type structure in Na+ solution. The result unveils an unusual multichannel nonradiative mechanism dominated by states with varying character of charge transfer lasting ten and hundreds of picoseconds, accounting altogether for an overwhelming ∼85% of the overall deactivation involving proton transfer. Our comparative study shows that encapsulating the GQ in nanocavity water pool or changing it into hydrid-type topologies with the presence of K+ ions alter differently energies and lifetimes of these states, yet without affecting the nature of the electronic excitation involved. The finding of this work underscores a leading role of structural rigidity in regulating the interplay with the microenvironment of photoexcited monomolecularly folded HT-GQs.

Activity with ambulation attenuates diuretic responsiveness in chronic heart failure.

INTRODUCTION: We hypothesized that discharged heart failure (HF) patients could develop clinical congestion despite adhering to prescribed diuretics, because ambulation attenuates diuretic and natriuretic responsiveness. METHODS: We studied 9 patients aged 57 ± 13 (mean ± SD) years with New York Heart Association functional class II-III symptoms and ejection fraction <40% (28 ± 7%) and receiving furosemide (≥80 mg/d [113 ± 53 mg/d]) plus renin-angiotensin system antagonists and beta-blockade. Inulin and p-amminohippuric acid were infused to estimate glomerular filtration rate (GFR) and renal plasma flow (RPF). Furosemide was administered intravenously at 75% of the usual oral morning dose. Participants were randomized to supine (90 minutes recumbancy) or upright (90 minutes sitting and treadmill walking) posture and assumed the other position on their second day. Primary outcome variables were urine volume and sodium excretion 90 minutes after furosemide. RESULTS: On the upright, compared with the supine, day, urine volume (792 ± 484 vs 1,290 ± 503 mL; P = .02) and sodium (79 ± 55 vs 141 ± 61 mmol; P < .01) were attenuated, whereas plasma norepinephrine (4.4 ± 2.7 vs 2.3 ± 1.8 mmol/L; P = .01) and renin (327 ± 250% of supine; P < .01) were augmented. Urinary K+, mean pressure, GFR, and RPF were similar. CONCLUSIONS: Activation of the sympathetic nervous system and renin-angiotensin axis by upright ambulation may attenuate diuresis and natriuresis by increasing proximal tubular reabsorption of sodium and water.

Abnormal nocturnal heart rate variability response among chronic kidney disease and dialysis patients during wakefulness and sleep.

BACKGROUND: Dialysis patients and patients with chronic kidney disease (CKD) experience a substantial risk for abnormal autonomic function and abnormal heart rate variability (HRV). It remains unknown whether HRV changes across sleep stages in patients with different severity of CKD or dialysis dependency. We hypothesized that high-frequency (HF) HRV (vagal tone) will be attenuated from wakefulness to non-rapid eye movement (NREM) and then to rapid eye movement (REM) sleep in dialysis patients as compared to patients with CKD. METHODS: In-home polysomnography was performed in 95 patients with stages 4-5 CKD or end-stage renal disease (ESRD) on haemodialysis (HD) or peritoneal dialysis (PD). HRV was measured using fast Fourier transform of interbeat intervals during wakefulness and sleep. Low-frequency (LF) and HF intervals were generated. Natural logarithm HF (LNHF) and the logarithm LF/HF ratio (sympathovagal tone) were analysed by multivariable quantile regression and generalized estimating equations. RESULTS: Of the 95 patients, 63.2% (n = 60) was male, 35.8% (n = 34) was African American and 20.4% (n = 19) was diabetic. Average age was 51.6 ± 15.1 (range 19-82). HRV variables were significantly associated with diabetic status, higher periodic limb movement indices and lower bicarbonate levels. Patients with advanced CKD did not differ from dialysis patients in their inability to increase vagal tone during sleep. During wakefulness, female gender (P = 0.05) was associated with the increases in the vagal tone. CONCLUSIONS: Patients with CKD/ESRD exhibit dysregulation of the autonomic nervous system tone manifesting as a failure to increase HRV during wakefulness and sleep. Different patient characteristics are associated with changes in HRV at different sleep stages.

Heart rate variability (HRV) in kidney failure: measurement and consequences of reduced HRV.

A common cause of death in end-stage renal disease (ESRD) patients on dialysis is sudden cardiac death (SCD). Compared to the general population, the percentage of cardiovascular deaths that are attributed to SCD is higher in patients treated by dialysis. While coronary artery disease (CAD) is the predominant cause of SCD in dialysis patients, reduced heart rate variability (HRV) may play a role in the higher risk of SCD among other risk factors. HRV refers to beat-to-beat alterations in heart rate as measured by periodic variation in the R-R interval. HRV provides a non-invasive method for investigating autonomic input into the heart. It quantifies the amount by which the R-R interval or heart rate changes from one cardiac cycle to the next. The autonomic nervous system transmits impulses from the central nervous system to peripheral organs and is responsible for controlling the heart rate, blood pressure and respiratory activity. In normal individuals, without cardiac disease, the heart rate has a high degree of beat-to-beat variability. HRV fluctuates with respiration: it increases with inspiration and decreases with expiration and is primarily mediated by parasympathetic activity. HRV has been used to evaluate and quantify the cardiac risk associated with a variety of conditions including cardiac disorders, stroke, multiple sclerosis and diabetes. In this narrative review, we will examine the association between HRV and SCD. This report explains the measurement of HRV and the consequences of reduced HRV in the general population and dialysis patients. Lastly, this review will outline the possible use of HRV as a clinical predictor for SCD in the dialysis population. The current understanding of SCD based on HRV findings among the ESRD population support the use of more aggressive treatment of CAD; greater use of angiotensin converting enzyme inhibitor (ACE-i)/angiotensin receptor blockers (ARBs) and beta-blockers and more frequent and/or nocturnal haemodialysis to improve the survival of a patient with kidney failure.