Activation of SIRT1 by l -serine increases fatty acid oxidation and reverses insulin resistance in C2C12 myotubes ( l -serine activates SIRT1 in C2C12 myotubes)

Abstract

Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, and the function is linked to cellular metabolism including mitochondrial biogenesis. Hepatic l-serine concentration is decreased significantly in fatty liver disease. We reported that the supplementation of the amino acid ameliorated the alcoholic fatty liver by enhancing l-serine-dependent homocysteine metabolism. In this study, we hypothesized that the metabolic production of NAD⁺ from l-serine and thus activation of SIRT1 contribute to the action of l-serine. To this end, we evaluated the effects of l-serine on SIRT1 activity and mitochondria biogenesis in C2C12 myotubes. l-Serine increased intracellular NAD⁺ content and led to the activation of SIRT1 as determined by p53 luciferase assay and western blot analysis of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) acetylation. l-Serine treatment increased the expression of the genes associated with mitochondrial biogenesis and enhanced mitochondrial mass and function. In addition, l-serine reversed cellular insulin resistance determined by insulin-induced phosphorylation of Akt and GLUT4 expression and membrane translocation. l-Serine-induced mitochondrial gene expression, fatty acid oxidation, and insulin sensitization were mediated by enhanced SIRT1 activity, which was verified by selective SIRT1 inhibitor (Ex-527) and siRNA directed to SIRT1. l-Serine effect on cellular NAD⁺ level is dependent on the l-serine metabolism to pyruvate that is subsequently converted to lactate by lactate dehydrogenase. In summary, these data suggest that l-serine increases cellular NAD⁺ level and thus SIRT1 activity in C2C12 myotubes.

http://bit.ly/2SaaQYc

Cotransport of Suspended Colloids and Nanoparticles in Porous Media

Abstract

The objective of this study is to develop a model for cotransport of colloids and nanoparticles (NPs) in porous media under two particle capture mechanisms. The particle capture rate is proportional to the capture probability, which is a function of retained concentration, called the filtration function. Laboratory bench-scale experiments of individual transport of NPs and colloidal-size kaolinite clay particles through packed columns produced breakthrough curves (BTCs) that monotonically increased with time and stabilised at some value lower than the injected concentration. We discuss the filtration function that corresponds to BTCs stabilising at the concentration lower than the injected value. This so-called binary filtration function incorporates two particle capture mechanisms. The analytical transport model with a binary filtration function was capable to fit successfully BTCs obtained from individual transport experiments using kaolinite and NPs conducted by Chrysikopoulos et al. (Transp Porous Med 119(1):181–204, 2017). Assuming that the electrostatic particle–solid matrix interaction and the fraction of the solid matrix surface area occupied by a single attached particle (kaolinite or NP) are the same for individual transport of either kaolinite particles or NPs and for simultaneous cotransport of kaolinite particles and NPs, the proposed binary filtration function was extended for the cotransport case. Although the breakthrough data from cotransport experiments with kaolinite particles and NPs have six degrees of freedom, the developed cotransport model successfully matches the BTCs by tuning two constants only. This validates the developed model for cotransport of two colloidal populations with different attachments and straining rates.

http://bit.ly/2ScqeTM

Observational study of newborn infant parasympathetic evaluation as a comfort system in awake patients admitted to a pediatric intensive care unit

Abstract

To compare the newborn infant parasympathetic evaluation system (NIPE) scores with a validated clinical scale using two different nebulizers in children with bronchiolitis admitted to a PICU. Comfort was evaluated using the COMFORT-behavior scale (CBS) before (T1), during (T2) and after (T3) each nebulization. In order to compare NIPE and CBS values during the whole T1 to T3 period, the variable Dif-CBS was defined as the difference between maximal and minimal CBS scores, and Dif-NIPE as the difference between 75th and 25th percentile NIPE values. Analyses were carried out, firstly for the total of nebulizations and secondly comparing two different nebulization systems: a jet nebulizer (JN) and a nebulizer integrated in high flow nasal cannulas (NHF). 84 nebulizations were recorded on 14 patients with a median [25th–75th percentile] age of 6 months (3.1–9.5). A Dif-CBS of 4 points (2–7), as well as changes in CBS scores between T1 and T2, defined the nebulization as a discomfort stimulus. The NIPE system, represented as the Dif-NIPE, showed a median variation of 9 points (7–10), and was poorly correlated to Dif-CBS [r_s 0.162 (P = 0.142)]. Discomfort during nebulization, assessed by CBS was greater with the JN system compared to NHF: 17 (13–22) vs 13 (9–15) (P = 0.001). NIPE monitoring detected no significant differences between both nebulization systems (P = 0.706). NIPE monitoring showed a variation in comfort during nebulization in the patient with bronchiolitis, though correlation with CBS was poor. Further research is required before NIPE can be suggested as a comfort monitoring system for the awake infant.

http://bit.ly/2WHu9XC

Acoustic Field of Phased-Array Ultrasound Transducer with the Focus/Foci Shifting

Abstract

Background

High-intensity focused ultrasound (HIFU) is becoming popular in the treatment of solid tumors because of its non-invasiveness with few complications. The acoustic field is of importance in evaluating the safe focus shifting distance and determining the treatment plan.

Methods

The propagation of finite-amplitude acoustic wave from a 331-element HIFU phased-array with focus steering along and transverse to the transducer axis and 4-foci shifting on the focal plane was simulated using the angular spectrum approach (ASA) with a marching second-order operator-splitting scheme. In addition, the acoustic field produced by a truncated asymmetric transesophageal HIFU annular array was also simulated, and the effects of driving frequency and the number of concentric rings were investigated.

Results

Because of the nonlinear effects, the peak negative pressure is lower than that of peak positive pressure at the main lobe but has a larger beam size. However, the peak positive and negative pressures at the grating lobe are quite similar. The effects of the focus shifting distances on the main and grating lobe (both acoustic pressure and − 6 dB beam size) were evaluated. With the focus shifting axially away from the transducer surface, the main lobe has decreased acoustic pressure by ~ 1.9 fold and increased beam size by ~ 4.5 fold while the grating lobe has the increased acoustic pressure by ~ 1.8 fold. The focus shifting laterally leads to the reduced pressure at the main lobe by ~ 1.4 fold but the slight decrease at the grating lobe by ~ 1.1 fold. In comparison, the shifting of multi-foci has similar influences on the main lobe but increases the pressure at the grating lobe. Driving frequency of annular array is found to have greater influences on the peak pressure and beam size.

Conclusion

Our algorithm can simulate the acoustic field of phased-array in arbitrary shape and optimize the transducer design, and the focus shifting distance and strategy should be selected appropriately for the safe HIFU exposure.

http://bit.ly/2RHpXDo

An exploratory clinical evaluation of a head-worn display based multiple-patient monitoring application: impact on supervising anesthesiologists’ situation awareness

Abstract

Purpose

Supervising anesthesiologists overseeing several operating rooms must be aware of the status of multiple patients, so they can consult with the anesthetist in single operating rooms or respond quickly to critical events. However, maintaining good situation awareness can be challenging when away from patient bedsides or a central monitoring station. In this proof-of-concept study, we evaluated the potential of a head-worn display that showed multiple patients' vital signs and alarms to improve supervising anesthesiologists' situation awareness.

Methods

Eight supervising anesthesiologists each monitored the vital signs of patients in six operating rooms for 3 h with the head-worn display, and for another 3 h without the head-worn display. In interviews with each anesthesiologist, we assessed in which situations the head-worn display was used and whether the continuous availability of the vital signs improved situation awareness. We also measured situation awareness quantitatively from six of the eight anesthesiologists, by instructing them to press a button whenever they noticed a patient alarm.

Results

The median number of patient alarms occurring was similar when the anesthesiologists monitored with the head-worn display (42.0) and without the head-worn display (40.5). However, the anesthesiologists noticed significantly more patient alarms with the head-worn display (66.7%) than without (7.1%), P = 0.028, and they reported improved situation awareness with the head-worn display. The head-worn display helped the anesthesiologists to perceive and comprehend patients' current status and to anticipate future developments. A negative effect of the head-worn display was its tendency to distract during demanding procedures.

Conclusions

Head-worn displays can improve supervising anesthesiologists' situation awareness in multiple-patient monitoring situations. The anesthesiologists who participated in the study expressed enthusiasm about monitoring patients with a head-worn display and wished to use and evaluate it further.

http://bit.ly/2UBlgNk

Assessment of the tau protein concentration in patients with tick-borne encephalitis

Abstract

There have been suggestions that tick-borne encephalitis (TBE) may cause neurodenenerative changes in the brain. The aim of this study was the assessment of the tau protein concentration in cerebrospinal fluid (CSF) of patients with different clinical forms of TBE. The concentration of tau protein in CSF was determined using Fujirebio tests (Ghent, Belgium) in 35 patients with TBE: group I—patients with meningitis (n = 16); group II—patients with meningoencephalitis (n = 19). None of the patients reported any neurodegenerative disorder that could affect the results of the study. The control group (CG) consisted of 10 patients in whom inflammatory process in central nervous system was excluded. Tau protein concentration in CSF before treatment did not differ significantly between the examined groups, while its concentration was significantly higher in encephalitis group than in CG after 14 days of treatment. Significant increase in tau protein concentration after treatment was observed in both examined groups. The comparison between the group of patients who fully recovered and patients who presented with persistent symptoms on discharge showed significant differences in tau protein concentration before and after treatment. ROC curve analysis indicates that CSF tau protein concentration before treatment may predict complicated course of the disease with 90.9% specificity and 80% sensitivity, while after treatment, specificity became 72.7% and 71.4% for sensitivity. Correlation analysis showed that in TBE patients (both meningoencephalitis and meningitis groups), CSF pleocytosis before treatment correlated negatively with tau protein concentration in CSF. (1) Neurodegeneration process is present in TBE encephalitis. (2) Tau protein concentration may be used as a predictor of complicated course of TBE.

http://bit.ly/2UHe1Dk

Announcement

http://bit.ly/2HSyzYc