Thermodynamic Study of Alkylsilane and Alkylsiloxane-Based Ionic Liquids.

The thermodynamic properties of ionic liquids (ILs) bearing alkylsilane and alkylsiloxane chains, as well as their carbon-based analogs, were investigated. Effects such as the replacement of carbon atoms by silicon atoms, the introduction of a siloxane linkage, and the length of the alkylsilane chain were explored. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to study the thermal and phase behavior (glass transition temperature, melting point, enthalpy and entropy of fusion, and thermal stability). Heat capacity was obtained by high-precision drop calorimetry and differential scanning microcalorimetry. The volatility and cohesive energy of these ILs were investigated via the Knudsen effusion method coupled with a quartz crystal microbalance (KEQCM). Gas phase energetics and structure were also studied to obtain the gas phase heat capacity as well as the energy profile associated with the rotation of the IL side chain. The computational study suggested the existence of an intramolecular interaction in the alkylsiloxane-based IL. The obtained glass transition temperatures seem to follow the trend of chain flexibility. An increase of the alkylsilane chain leads to a seemingly linear increase in molar heat capacity. A regular increment of 30 J·K-1·mol-1 in the molar heat capacity was found for the replacement of carbon by silicon in the IL alkyl chain. The alkylsilane series was revealed to be slightly more volatile than its carbon-based analogs. A further increase in volatility was found for the alkylsiloxane-based IL, which is likely related to the decrease of the cohesive energy due to the existence of an intramolecular interaction between the siloxane linkage and the imidazolium headgroup. The use of Si in the IL structure is a suitable way to significantly reduce the IL's viscosity while preserving its large liquid range (low melting point and high thermal stability) and low volatilities.

Extensive characterization of choline chloride and its solid-liquid equilibrium with water.

The importance of choline chloride (ChCl) is recognized due to its widespread use in the formulation of deep eutectic solvents. The controlled addition of water in deep eutectic solvents has been proposed to overcome some of the major drawbacks of these solvents, namely their high hygroscopicities and viscosities. Recently, aqueous solutions of ChCl at specific mole ratios have been presented as a novel, low viscous deep eutectic solvent. Nevertheless, these proposals are suggested without any information about the solid-liquid phase diagram of this system or the deviations from the thermodynamic ideality of its precursors. This work contributes significantly to this matter as the phase behavior of pure ChCl and (ChCl + H2O) binary mixtures was investigated by calorimetric and analytical techniques. The thermal behavior and stability of ChCl were studied by polarized light optical microscopy and differential scanning calorimetry, confirming the existence of a solid-solid transition at 352.2 ± 0.6 K. Additionally, heat capacity measurements of pure ChCl (covering both ChCl solid phases) and aqueous solutions of ChCl (xChCl < 0.4) were performed using a heat-flow differential scanning microcalorimeter or a high-precision heat capacity drop calorimeter, allowing the estimation of a heat capacity change of (ChCl) ≈ 39.3 ± 10 J K-1 mol-1, between the hypothetical liquid and the observed crystalline phase at 298.15 K. The solid-liquid phase diagram of the ChCl + water mixture was investigated in the whole concentration range by differential scanning calorimetry and the analytical shake-flask method. The phase diagram obtained for the mixture shows an eutectic temperature of 204 K, at a mole fraction of choline chloride close to xChCl = 0.2, and a shift of the solid-solid transition of ChCl-water mixtures of 10 K below the value observed for pure choline chloride, suggesting the appearance of a new crystalline structure of ChCl in the presence of water, as confirmed by X-ray diffraction. The liquid phase presents significant negative deviations to ideality for water while COSMO-RS predicts a near ideal behaviour for ChCl.

International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis.

OBJECTIVE: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. METHODS: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. RESULTS: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). CONCLUSION: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.

PANRETINAL RITONAVIR-INDUCED RETINOPATHY: A REPORT OF LONG-TERM USE.

PURPOSE: To report a case involving a patient with presumed panretinal ritonavir-induced retinopathy. METHODS: A 52-year-old, HIV-positive patient, with no criteria for AIDS associated with the use of ritonavir for more than 10 years, underwent clinical examination, fundus photography, spectral domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: Fundus examination revealed areas of atrophy and hypertrophy in the retinal pigment epithelium throughout the retina. Laboratory tests for other diseases were all negative. CONCLUSION: HIV-positive patients undergoing ritonavir therapy should be carefully followed in the presence of low-acuity vision complaints and retinal changes.

Effects of subcutaneous injection of ozone during wound healing in rats.

Fibroblast growth factor 2 (FGF2) regulates the wound repair process and it is secreted by inflammatory and endothelial cells, and by myofibroblasts. This study aimed to establish the expression patterns of FGF2 and myofibroblastic differentiation during wound healing in rats treated with subcutaneous ozone injection. We created full-thickness excisional wounds in rats, and the healing process was analyzed through morphometric analyses and digital quantification of immunoreactivity of smooth muscle actin and FGF2. Ozone therapy-treated wounds presented granulation tissue with a reduced number of inflammatory cells and greater dermal cellularity, and intense collagen deposition. FGF2 immunoreactivity, microvessel density, and amount of myofibroblasts were significantly higher in treated wounds compared to controls. In conclusion, it was demonstrated that subcutaneous injections of ozone accelerate and ameliorate wound repairing process. Moreover, injectable ozone therapy's action mechanism may be associated with FGF2 overexpression.

Myclobutanil enantioselective risk assessment in humans through in vitro CYP450 reactions: Metabolism and inhibition studies.

Myclobutanil is a chiral triazole fungicide that is employed worldwide. Although enantiomers have the same physical-chemical properties, they may differ in terms of activity, metabolism, and toxicity. This investigation consisted of in vitro enantioselective metabolism studies that employed a human model to assess the risks of myclobutanil in humans. A LC-MS/MS enantioselective method was developed and validated. The enzymatic kinetic parameters (VMAX, KMapp, and CLINT) determined for in vitro rac-myclobutanil and S-(+)-myclobutanil metabolism revealed enantioselective differences. Furthermore, human CYP450 enzymes did not metabolize R-(-)-myclobutanil. The predicted in vivo toxicokinetic parameters indicated that S-(+)-myclobutanil may be preferentially eliminated by the liver and suffer the first-pass metabolism effect. However, because CYP450 did not metabolize R-(-)-myclobutanil, this enantiomer could reach the systemic circulation and stay longer in the human body, potentially causing toxic effects. The CYP450 isoforms CYP2C19 and CYP3A4 were involved in rac-myclobutanil and S-(+)-myclobutanil metabolism. Although there were differences in the metabolism of the myclobutanil enantiomers, in vitro inhibition studies did not show significant enantioselective differences. Overall, the present investigation suggested that myclobutanil moderately inhibits CYP2D6 and CYP2C9 in vitro and strongly inhibits CYP3A and CYP2C19 in vitro. These results provide useful scientific information for myclobutanil risk assessment in humans.

Optimal Interval for Success in Judo World-Ranking Competitions.

PURPOSE: To determine the optimal interval between competitions for success in the different events of the judo world tour. METHODS: A total of 20,916 female and 29,900 male competition participations in the judo world-tour competitions held between January 2009 and December 2015 were analyzed, considering the dependent variable, winning a medal, and the independent variables, levels of competition. RESULTS: There was an increased probability of winning a medal when the interval was in the 10- to 13-wk range for both male and female athletes competing at Grand Prix, Continental-Championship, and World-Championship events, whereas for Grand Slam, only men had an increased probability of winning a medal in this interval range. Furthermore, men had increased probability of podium positions in Continental Championship, World Master, and Olympic Games when the interval was longer than 14 wk. CONCLUSION: Optimal interval period between successive competitions varies according to competition level and sex; shorter intervals (6-9 wk) were better for female athletes competing at the lowest competition level (Continental Open), but for most of the competitions, the 10- to 13-wk interval was detected as optimal for both male and female athletes (Grand Prix, Continental Championship, and World Championship), whereas for the ranking-based qualified male competitions (ie, Masters and Olympic Games), a longer period (>14 wk) is needed.

High IL-10 production by aged AIDS patients is related to high frequency of Tr-1 phenotype and low in vitro viral replication.

This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4(+)FoxP3(+)CD25(+)Treg cells in this patient group, high frequencies of IL-10-producing CD4(+)FoxP3(-) T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4(+)FoxP3(-)CD152(+) T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1ß by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals.