Cholesterol efflux alterations in adolescent obesity: role of adipose-derived extracellular vesical microRNAs.

BACKGROUND: Macrophage cholesterol efflux capacity has been identified as a predictor for cardiovascular disease. We assessed the relationship between adipocyte-derived extracellular vesicle microRNAs and macrophage cholesterol efflux capacity. METHODS: We assessed an adolescent cohort (n = 93, Age, median (IQR) = 17 (3) year, Female = 71, Male = 22) throughout the BMI continuum (BMI = 45.2 (13.2) kg/m2) for: (1) cholesterol efflux capacity and lipoprotein profiles; (2) adipocyte-derived extracellular vesicle microRNAs in serum; (3) the role of visceral adipose tissue extracellular vesicle in regulation of cholesterol efflux and cholesterol efflux gene expression in THP-1 macrophages in vitro. RESULTS: Efflux capacity was significantly associated with HDL (r = 0.30, p = 0.01) and LDL (r = 0.33, p = 0.005) particle size. Multivariate-analysis identified six microRNAs associated (p < 0.05) with cholesterol efflux capacity: miR-3129-5p (Beta = 0.695), miR-20b (0.430), miR9-5p (0.111), miR-320d (- 0.190), miR301a-5p (0.042), miR-155-5p (0.004). In response to increasing concentrations (1 µg/mL vs. 3 µg/mL) of VAT extracellular vesicle, cholesterol efflux (66% ± 10% vs. 49% ± 2%; p < 0.01) and expression of ABCA1 (FC = 1.9 ± 0.8 vs 0.5 ± 0.2; p < 0.001), CD36 (0.7 ± 0.4 vs. 2.1 ± 0.8, p = 0.02), CYP27A1 (1.4 ± 0.4 vs. 0.9 ± 0.5; p < 0.05), and LXRA (1.8 ± 1.1 vs. 0.5 ± 0.2; p < 0.05) was altered in THP-1 cells in vitro. CONCLUSION: Adipocyte-derived extracellular vesicle microRNAs may, in part, be involved macrophage cholesterol efflux regulation.

Macrophage lipid accumulation in the presence of immunosuppressive drugs mycophenolate mofetil and cyclosporin A.

OBJECTIVE: Mycophenolate (MPA) and cyclosporin A (CsA) are two immunosuppressive agents currently used for the treatment of autoimmune diseases. However, reports regarding their effects on inflammation and lipid handling are controversial. Here, we compare the effect of these two drugs on the expression of proteins involved in cholesterol handling and lipid accumulation in a macrophage cell system utilizing M0, M1 and M2 human macrophages and in murine bone marrow-derived macrophages (BMDM). METHODS: Differentiated M0, M1 and M2 subsets of THP-1 human macrophages were subjected to various concentrations of either MPA or CsA. Expression of proteins involved in reverse cholesterol transport (ABCA1 and 27-hydroxylase) and scavenger receptors, responsible for uptake of modified lipids (CD36, ScR-A1, CXCL16 and LOX-1), were evaluated by real-time PCR and confirmed with Western blot. DiI-oxidized LDL internalization assay was used to assess foam cell formation. The influence of MPA was also evaluated in BMDM obtained from atherosclerosis-prone transgenic mice, ApoE-/- and ApoE-/-Fas-/-. RESULTS: In M0 macrophages, MPA increased expression of ABCA1 and CXCL16 in a concentration-dependent manner. In M1 THP-1 macrophages, MPA caused a significant increase of 27-hydroxylase mRNA and CD36 and SR-A1 receptor mRNAs. Exposure of M2 macrophages to MPA also stimulated expression of 27-hydroxylase, while downregulating all evaluated scavenger receptors. In contrast, CsA had no impact on cholesterol efflux in M0 and M1 macrophages, but significantly augmented expression of ABCA1 and 27-hydroxylase in M2 macrophages. CsA significantly increased expression of the LOX1 receptor in naïve macrophages, downregulated expression of CD36 and SR-A1 in the M1 subpopulation and upregulated expression of all evaluated scavenger receptors. However, CsA enhanced foam cell transformation in M0 and M2 macrophages, while MPA had no effect on foam cell formation unless used at a high concentration in the M2 subtype. CONCLUSIONS: Our results clearly underline the importance of further evaluation of the effects of these drugs when used in atherosclerosis-prone patients with autoimmune or renal disease.

2,4-Dimethoxy-2,4-dimethylpentan-3-one: An Aprotic Solvent Designed for Stability in Li-O2 Cells.

In this study, we present a new aprotic solvent, 2,4-dimethoxy-2,4-dimethylpentan-3-one (DMDMP), which is designed to resist nucleophilic attack and hydrogen abstraction by reduced oxygen species. Li-O2 cells using DMDMP solutions were successfully cycled. By various analytical measurements, we showed that even after prolonged cycling only a negligible amount of DMDMP was degraded. We suggest that the observed capacity fading of the Li-O2 DMDMP-based cells was due to instability of the lithium anode during cycling. The stability toward oxygen species makes DMDMP an excellent solvent candidate for many kinds of electrochemical systems which involve oxygen reduction and assorted evaluation reactions.

Hexafluorophosphate-Based Solutions for Mg Batteries and the Importance of Chlorides.

The selection of viable conventional magnesium salts in electrolyte solutions for Mg secondary batteries is very limited. Reversible magnesium deposition was demonstrated with only MgTFSI2, in ethereal solutions. A recent report has suggested that Mg can be reversibly deposited from a solution of Mg(PF6)2 in tetrahydrofuran and acetonitrile. In this paper, we dispute that claim and show that PF6- anions passivate Mg anodes and completely inhibit any Mg deposition/dissolution process. We show that addition of chlorides suppresses the passivation phenomena and allows reversible Mg deposition/dissolution processes to commence. The Mg deposits have been examined via elemental analysis, scanning electron microscopy, and X-ray diffraction measurements, depicting a highly oriented, preferential Mg growth. This study evaluates the feasibility of employing PF6-based electrolytes for Mg batteries and exemplifies the aptitude of chlorides for suppressing passivation phenomena.

The High Performance of Crystal Water Containing Manganese Birnessite Cathodes for Magnesium Batteries.

Rechargeable magnesium batteries have lately received great attention for large-scale energy storage systems due to their high volumetric capacities, low materials cost, and safe characteristic. However, the bivalency of Mg(2+) ions has made it challenging to find cathode materials operating at high voltages with decent (de)intercalation kinetics. In an effort to overcome this challenge, we adopt an unconventional approach of engaging crystal water in the layered structure of Birnessite MnO2 because the crystal water can effectively screen electrostatic interactions between Mg(2+) ions and the host anions. The crucial role of the crystal water was revealed by directly visualizing its presence and dynamic rearrangement using scanning transmission electron microscopy (STEM). Moreover, the importance of lowering desolvation energy penalty at the cathode-electrolyte interface was elucidated by working with water containing nonaqueous electrolytes. In aqueous electrolytes, the decreased interfacial energy penalty by hydration of Mg(2+) allows Birnessite MnO2 to achieve a large reversible capacity (231.1 mAh g(-1)) at high operating voltage (2.8 V vs Mg/Mg(2+)) with excellent cycle life (62.5% retention after 10000 cycles), unveiling the importance of effective charge shielding in the host and facile Mg(2+) ions transfer through the cathode's interface.

The Rise of Endovascular Mechanical Circulatory Support Use for Cardiogenic Shock and High Risk Coronary Intervention: Considerations and Challenges.

Introduction: Cardiogenic shock due to acute myocardial infarction and decompensated advanced heart failure remains a source of significant morbidity and mortality. Endovascular mechanical circulatory support devices including intra-aortic balloon pump (IABP), percutaneous left ventricular assist devices (Impella and Tandemheart pumps), and veno-arterial extracorporeal oxygenation (VA-ECMO) are utilized for a broadening range of indications.Areas covered: This narrative review explores the specific devices, their distinctive hemodynamic profiles, and practical considerations. Furthermore, reviewed are the trials evaluating device outcomes which have generated significant controversy within the field of heart failure and shock. New applications and future directions are discussed.Expert opinion: Use of endovascular mechanical circulatory support has increased over the last decade, though evidence supporting their use is lacking. Development of large-scale prospective registries and clinical classification systems will facilitate patient enrollment and inform trial design. Furthermore, expansion of indications for these devices is revolutionizing how the field of heart failure and cardiogenic shock thinks about hemodynamic support. The ability to tailor therapy to a patient's specific hemodynamic profile appears to be the future of cardiogenic shock management.

The Power of Stoichiometry: Conditioning and Speciation of MgCl2/AlCl3 in Tetraethylene Glycol Dimethyl Ether-Based Electrolytes.

In many Mg-based battery systems, the reversibility of Mg deposition and dissolution is lowered by parasitic formation processes of the electrolyte. Therefore, high Coulombic efficiencies of Mg deposition and dissolution are only achieved after several "conditioning" cycles. As this phenomenon is especially reported for AlCl3-containing solutions, this study focuses on the "conditioning" mechanisms of MgCl2/AlCl3 and MgHMDS2/AlCl3 (HMDS = hexamethyldisilazide) in tetraethylene glycol dimethyl ether (TEGDME)-based electrolytes. Electrochemical (cyclic voltammetry) and spectroscopic investigations (27Al nuclear magnetic resonance spectroscopy, Raman spectroscopy, inductively coupled plasma optical emission spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy) reveal that cationic AlCl2+ species in TEGDME-based electrolytes with an AlCl3/MgCl2 ratio higher than 1:1 corrode the Mg metal. According to a cementation reaction mechanism, the corrosion of Mg is accompanied with Al deposition. In effect, the consumption of Mg results in low Coulombic efficiencies of Mg deposition and dissolution during the electrolyte "conditioning". After understanding the mechanism of this process, we demonstrate that a careful adjustment of the stoichiometry in MgCl2/AlCl3 and MgHMDS2/AlCl3 in TEGDME formulations prevents Mg corrosion and results in "conditioning"-free, highly efficient Mg deposition and dissolution.

On the Feasibility of Practical Mg-S Batteries: Practical Limitations Associated with Metallic Magnesium Anodes.

Rechargeable magnesium batteries (RMBs) have attracted a lot of attention in recent decades due to the theoretical properties of these systems in terms of energy density, safety, and price. Nevertheless, to date, fully rechargeable magnesium battery prototypes with sufficient longevity and reversibility were realized only with low voltage and low capacity intercalation cathode materials based on Cheverel phases. The community is therefore actively looking for high-capacity cathodes that can work with metallic magnesium anodes in viable RMB systems. One of the most promising cathode materials, in terms of very high theoretical specific capacity, is, naturally, sulfur. A number of recent works studied the electrochemical performances of rechargeable sulfur cathodes in RMB, with success to some extent on the cathode side. Nevertheless, as known from the lithium-sulfur rechargeable battery systems, the formation of soluble polysulfides during discharge affects strongly the behavior of the anode side. In this article and the work it describes, we focus on  soluble polysulfides impact on Mg-S electrochemichal systems. We carefully designed herein conditions that mimic the Mg-S battery prototypes containing balanced Mg and elemental sulfur electrodes. Under these conditions, we extensively studied the Mg anode behavior. The study shows that when elemental sulfur cathodes are discharged in the Mg-S cells containing electrolyte solutions in which Mg anodes behave reversibly, the polysulfide species thus formed migrate to the anode and eventually fully passivate it by the formation of very stable surface layers. The work involved electrochemical, spectroscopic, and microscopic studies. The present study clearly shows that to realize practical rechargeable Mg-S batteries, the transport of any sulfide moieties from the sulfur cathode to the magnesium anode has to be completely avoided. Such a condition is mandatory for the operation of secondary Mg-S batteries.

Mechanistic Role of Li⁺ Dissociation Level in Aprotic Li-O2 Battery.

The kinetics and thermodynamics of oxygen reduction reactions (ORR) in aprotic Li electrolyte were shown to be highly dependent on the surrounding chemical environment and electrochemical conditions. Numerous reports have demonstrated the importance of high donor number (DN) solvents for enhanced ORR, and attributed this phenomenon to the stabilizing interactions between the reduced oxygen species and the solvent molecules. We focus herein on the often overlooked effect of the Li salt used in the electrolyte solution. We show that the level of dissociation of the salt used plays a significant role in the ORR, even as important as the effect of the solvent DN. We clearly show that the salt used dictates the kinetics and thermodynamic of the ORR, and also enables control of the reduced Li2O2 morphology. By optimizing the salt composition, we have managed to demonstrate a superior ORR behavior in diglyme solutions, even when compared to the high DN DMSO solutions. Our work paves the way for optimization of various solvents with reasonable anodic and cathodic stabilities, which have so far been overlooked due to their relatively low DN.

Predictors of sustaining burn injury: does the use of common prevention strategies matter?

The incidence of burn injury has decreased over the past several decades. Although this has been largely attributed to increased prevention awareness, few studies evaluate the effectiveness of implementing standard burn prevention strategies in preventing burn injury. The authors hypothesized that patients who sustain burns use burn prevention strategies less frequently than those who do not. This was a case-control study composed of a prospective survey questionnaire and retrospective burn registry query, which was performed in a suburban academic medical center with a burn unit. All burn patients seen by the burn service in the year 2008 and a nonrandom sample of nonburned emergency department patients and visitors during the same time period were enrolled. Demographics included age, gender, income, education, house type, insurance status, and prevention strategy usage including smoke alarms, carbon monoxide detectors, fire extinguishers, and escape plans. The primary outcome of interest in this study was burn injury. Chi-square tests were used to compare rates, Student's t-tests were used to compare mean values of continuous variables between burn patients and others, and multivariate logistic regression was used to determine the strongest predictors of sustaining burn injury. One hundred ninety-four burn patients and 348 nonburned emergency department patients and visitors were surveyed. Burn patients reported the same rates of smoke alarm usage (96.9 vs 96.3%, P = .692), carbon monoxide detectors (75.3 vs 67.2%, P = .05), and higher rates of fire extinguisher ownership (80.4 vs 72.7%, P = .045) when compared with others. In multivariable analysis, the strongest predictor of sustaining burn injury was less than high school education (odds ratio [OR] 3.61, 95% confidence interval [CI] 1.27-10.27), whereas English as a primary language (OR 0.48, 95% CI 0.26-0.89), a graduate degree (OR 0.10, 95% CI 0.02-0.42), income >$50,000 (OR 0.46, 95% CI 0.29-0.72), and keeping flammable liquids in a locked place (OR 0.59, 95% CI 0.44-0.80) were protective against burn injury. Smoke alarms (OR 0.75, 95% CI 0.22-2.61), fire extinguishers (OR 1.34, 95% CI 0.80-2.32), and having an escape plan (OR 0.85, 95% CI 0.56-1.29) were not protective. Patients who sustain burn injury use burn prevention strategies at similar rates when compared with those who do not. When holding demographic characteristics constant, utilization of most burn prevention strategies is not protective of sustaining burn injury. Those with lower levels of education and income remain more susceptible to burn injury.

Rates of compliance with first aid recommendations in burn patients.

Several techniques (such as cooling and covering) are recommended in the first aid management of burn injured patients, both for lay persons and for EMS. Few studies have examined the rates of compliance with these recommendations. This study is a burn registry query performed in a suburban academic medical center with a regional burn unit. Patients seen by the burn service between January 2008 and February 2009 were included. Demographics, injury characteristics, rates of implementation of first aid, and method of transport to medical care (self vs ambulance) were recorded. Rates of implementation are reported as proportions with confidence intervals (CIs) and rates of implementation in those transported by self vs ambulance and work-related vs nonwork-related burns are compared using chi tests. Two hundred eleven burn patients were entered in the registry during the study period. Mean age was 27.0 (SD, 22.1) years, 44.3% were female, 95.2% were thermal burns, and 29.9% were transported by ambulance; 72.7% (95% CI, 66-78%) reported cooling their burn before presentation for medical care. Of those, 39.9% reported using tap water to cool their burn (95% CI, 33.4-46.8%), whereas 25.2% used ice (95% CI, 18.4-33.5%), and 8.9% used a cooling blanket (95% CI, 5-15%). Only 22.2% reported having applied a dressing before arrival in the hospital (95% CI, 16.9-28.5%). There were no significant differences between the groups who transported themselves to care in comparison with those who were brought in by ambulance in terms of cooling with water (P = .516), cooling with ice (P = .063), or application of dressing (P = .506). Further, no differences existed between those reporting cooling of the burn and those who did not in terms of patient characteristics. Rates of first aid administered for burn injury by lay persons before arrival at a burn center are high. A substantial percentage of people continue to use ice to cool their burns despite evidence of its potential detrimental nature. There is no difference in the rates of first aid implementation in those who did and did not contact EMS. The initial call to EMS might be used to instruct lay persons in appropriate burn first aid while awaiting the ambulance.