The Role of Left Ventricular Outflow Tract Peak Velocity Measurement in Patients With Sepsis and Septic Shock.

Aim To determine whether left ventricular outflow tract peak velocity is useful for the prediction of mortality in the early phase of sepsis or septic shock. Materials and methods Patients who were hospitalized in the emergency intensive care unit (ED-ICU) with the diagnosis of sepsis or septic shock were consecutively enrolled into two groups (sepsis and septic shock groups) between January 2020 to February 2021. Patients who are pregnant and ≤18 years old were excluded. Demographics, vital parameters, the presence of mechanical ventilation, and vasopressor/inotropic support with the doses of the drugs used were recorded. Ultrasonographic measurements included bedside caval indexes and left ventricular outflow tract (LVOT) peak velocity measurements. The primary outcome was in-hospital and 28th-day mortality. Results A total of 116 patients with a median age of 72.5 (27 to 96) years were enrolled. Sixty-eight (58.6%) patients were male. According to a receiver operating characteristic (ROC) curve analysis, 75 cm/s was determined as a cut-off value to determine the efficacy of LVOT peak velocity measurement for discriminating septic shock from sepsis and predicting 28-day and in-hospital mortality. The patients were then regrouped as 54 (46.5%) patients in low and 62 (53.5%) patients in high-velocity groups according to the cut-off value. Both in-hospital and 28th-day mortality rates were significantly different between these groups (p<0.001). Conclusion Left ventricular outflow tract peak velocity measurement may be a useful adjunct for the prediction of mortality in septic patients. Vasopressors and volume status of the patient do not affect LVOT peak velocity measurements.

Dissecting the effect of anions on Hg2+ detection using a FRET based DNA probe.

Many biosensors have been developed to detect Hg(2+) using thymine-rich DNA. While sensor response to various cations is often studied to demonstrate selectivity, the effect of anions has been largely overlooked. Anions may compete with DNA for metal binding and thus produce a false negative result. Anions cannot be added alone; the cation part of a salt may cause DNA compaction and other effects, obscuring the role of anions. We find that the sensitivity of a FRET-based Hg(2+) probe is independent of Na(+) concentration. Therefore, by using various sodium salts, any change in sensitivity can be attributed solely to the effect of anions. Halide salts, sulfides, and amines are strong inhibitors; anions containing oxo or hydroxyl groups (e.g. nitrate, sulfate, phosphate, carbonate, acetate, and citrate) do not interfere with Hg(2+) detection even at 100 mM concentration. Mercury hydrolysis and its diffusion into polypropylene containers can also strongly affect the detection results. We conclude that thymine-rich DNA should be useful for Hg(2+) detection in many environmental water samples.

Metal-induced specific and nonspecific oligonucleotide folding studied by FRET and related biophysical and bioanalytical implications.

Metal induced nucleic acid folding has been extensively studied with ribozymes, DNAzymes, tRNA and riboswitches. These RNA/DNA molecules usually have a high content of double-stranded regions to support a rigid scaffold. On the other hand, such rigid structural features are not available for many in vitro selected or rationally designed DNA aptamers; they adopt flexible random coil structures in the absence of target molecules. Upon target binding, these aptamers adaptively fold into a compact structure with a reduced end-to-end distance, making fluorescence resonance energy transfer (FRET) a popular signaling mechanism. However, nonspecific folding induced by mono- or divalent metal ions can also reduce the end-to-end distance and thus lead to false positive results. In this study we used a FRET pair labeled Hg(II) binding DNA and monitored metal-induced folding in the presence of various cations. While nonspecific electrostatically mediated folding can be very significant, at each tested salt condition, Hg(II) induced folding was still observed with a similar sensitivity. We also studied the biophysical meaning of the acceptor/donor fluorescence ratio that allowed us to explain the experimental observations. Potential solutions for this ionic strength problem have been discussed. For example, probes designed to signal the formation of double-stranded DNA showed a lower dependency on ionic strength.