The upper-airway microbiome as a biomarker of asthma exacerbations despite inhaled corticosteroid treatment.

BACKGROUND: The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. METHODS: Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. RESULTS: In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤ .037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤ .046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10-12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUCtraining: 0.82 and AUCvalidation: 0.77). CONCLUSION: The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS.

Human genetics influences microbiome composition involved in asthma exacerbations despite inhaled corticosteroid treatment.

BACKGROUND: The upper-airway microbiome is involved in asthma exacerbations despite inhaled corticosteroid (ICS) treatment. Although human genetics regulates microbiome composition, its influence on asthma-related airway bacteria remains unknown. OBJECTIVE: We sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma exacerbations and ICS response. METHODS: Saliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association of 6,296,951 genetic variants with exacerbation-related microbiome traits despite ICS treatment was tested through microbiome genome-wide association studies. Variants with 1 × 10-4 

Structural empowerment, personal initiative, and job satisfaction in service employees: Exploring the mediating role of psychological empowerment.

INTRODUCTION: This study explores how empowering human resource management (HRM) practices based on structural empowerment (access to opportunities, resources, support, and information) affect both personal initiative and job satisfaction of service employees through individual-level factors (psychological empowerment). METHODS: We conducted a cross-sectional survey study and collected 439 valid responses from service employees in Spain. The hypotheses were tested using structural equation modeling (SEM) with confidence intervals based on 10,000 resamples (i.e., bootstrapping technique). RESULTS: Our results showed that psychological empowerment partially mediated the relationship between structural empowerment and job satisfaction. It also fully mediated the relationship between structural empowerment and personal initiative at work. CONCLUSION: These findings emphasize the importance of HRM practices that can empower employees as key determinants of job satisfaction and personal initiative at service companies. Furthermore, a structural empowerment approach is a valid theoretical framework for studying and understanding employees' affective evaluations of work and, more specifically, their personal initiative.

Admixture mapping of severe asthma exacerbations in Hispanic/Latino children and youth.

BACKGROUND: In the USA, genetically admixed populations have the highest asthma prevalence and severe asthma exacerbations rates. This could be explained not only by environmental factors but also by genetic variants that exert ethnic-specific effects. However, no admixture mapping has been performed for severe asthma exacerbations. OBJECTIVE: We sought to identify genetic variants associated with severe asthma exacerbations in Hispanic/Latino subgroups by means of admixture mapping analyses and fine mapping, and to assess their transferability to other populations and potential functional roles. METHODS: We performed an admixture mapping in 1124 Puerto Rican and 625 Mexican American children with asthma. Fine-mapping of the significant peaks was performed via allelic testing of common and rare variants. We performed replication across Hispanic/Latino subgroups, and the transferability to non-Hispanic/Latino populations was assessed in 1001 African Americans, 1250 Singaporeans and 941 Europeans with asthma. The effects of the variants on gene expression and DNA methylation from whole blood were also evaluated in participants with asthma and in silico with data obtained through public databases. RESULTS: Genomewide significant associations of Indigenous American ancestry with severe asthma exacerbations were found at 5q32 in Mexican Americans as well as at 13q13-q13.2 and 3p13 in Puerto Ricans. The single nucleotide polymorphism (SNP) rs1144986 (C5orf46) showed consistent effects for severe asthma exacerbations across Hispanic/Latino subgroups, but it was not validated in non-Hispanics/Latinos. This SNP was associated with DPYSL3 DNA methylation and SCGB3A2 gene expression levels. CONCLUSIONS: Admixture mapping study of asthma exacerbations revealed a novel locus that exhibited Hispanic/Latino-specific effects and regulated DPYSL3 and SCGB3A2.

Multi-ancestry genome-wide association study of asthma exacerbations.

BACKGROUND: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. METHODS: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10-5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. RESULTS: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele ) = 0.82, p = 9.05 × 10-6 and replication: ORT allele  = 0.89, p = 5.35 × 10-3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele  = 0.85, p = 3.10 × 10-5 and replication: ORC allele  = 0.89, p = 1.30 × 10-2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. CONCLUSIONS: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Personal Beliefs about Illness Questionnaire-Revised (PBIQ-R): Spanish adaptation in a clinical sample with psychotic disorders.

BACKGROUND: The way people with psychosis psychologically adapt and manage the diagnosis of such a mental disorder has been considered a key factor that contributes to the emergence and aggravation of emotional problems. These beliefs about illness can be very important due to their possible association with stigma and its implications in terms of loss of roles and social status. Given the importance of these personal beliefs about the specific diagnosis of psychosis, the Personal Beliefs about Illness Questionnaire (PBIQ) and PBIQ-R have been developed. AIMS: The present study aims to explore the psychometric characteristics of the Spanish version of the PBIQ-R in a sample of patients with a diagnosis of psychosis-related disorders. METHOD: Participants were 155 patients (54.8% male) of the Public Health Service in Andalusia (Spain). Those who consented to participate filled in the PBIQ-R, the Social Comparison Scale, and the PHQ-9 and GAD-7 to measure emotional symptoms. RESULTS: All dimensions showed adequate internal consistency values: Cronbach's alpha extends between .81 and .88; and McDonald's omega ranges between .87 and .92. The temporal reliability for an interval of 3-4 weeks was high. The correlations between the PBIQ-R dimensions and the other variables included in the study were significant and in the expected direction. The factor analysis of the principal components of the PBIQ-R dimensions revealed a single factor in each of the dimensions that explained 64-74%. CONCLUSIONS: The results support the reliability and validity of the Spanish version of the PBIQ-R.

Aromatic Dimer Dehydrogenases from Novosphingobium aromaticivorans Reduce Monoaromatic Diketones.

Lignin is a potential source of valuable chemicals, but its chemical depolymerization results in a heterogeneous mixture of aromatics and other products. Microbes could valorize depolymerized lignin by converting multiple substrates into one or a small number of products. In this study, we describe the ability of Novosphingobium aromaticivorans to metabolize 1-(4-hydroxy-3-methoxyphenyl)propane-1,2-dione (G-diketone), an aromatic Hibbert diketone that is produced during formic acid-catalyzed lignin depolymerization. By assaying genome-wide transcript levels from N. aromaticivorans during growth on G-diketone and other chemically-related aromatics, we hypothesized that the Lig dehydrogenases, previously characterized as oxidizing ß-O-4 linkages in aromatic dimers, were involved in G-diketone metabolism by N. aromaticivorans. Using purified N. aromaticivorans Lig dehydrogenases, we found that LigL, LigN, and LigD each reduced the Cα ketone of G-diketone in vitro but with different substrate specificities and rates. Furthermore, LigL, but not LigN or LigD, also reduced the Cα ketone of 2-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one (GP-1) in vitro, a derivative of G-diketone with the Cß ketone reduced, when GP-1 was provided as a substrate. The newly identified activity of these Lig dehydrogenases expands the potential range of substrates utilized by N. aromaticivorans beyond what has been previously recognized. This is beneficial both for metabolizing a wide range of natural and non-native depolymerized lignin substrates and for engineering microbes and enzymes that are active with a broader range of aromatic compounds. IMPORTANCE Lignin is a major plant polymer composed of aromatic units that have value as chemicals. However, the structure and composition of lignin have made it difficult to use this polymer as a renewable source of industrial chemicals. Bacteria like Novosphingobium aromaticivorans have the potential to make chemicals from lignin not only because of their natural ability to metabolize a variety of aromatics but also because there are established protocols to engineer N. aromaticivorans strains to funnel lignin-derived aromatics into valuable products. In this work, we report a newly discovered activity of previously characterized dehydrogenase enzymes with a chemically modified by-product of lignin depolymerization. We propose that the activity of N. aromaticivorans enzymes with both native lignin aromatics and those produced by chemical depolymerization will expand opportunities for producing industrial chemicals from the heterogenous components of this abundant plant polymer.

Redundancy in aromatic O-demethylation and ring opening reactions in Novosphingobium aromaticivorans and their impact in the metabolism of plant derived phenolics.

Lignin is a plant heteropolymer composed of phenolic subunits. Because of its heterogeneity and recalcitrance, the development of efficient methods for its valorization still remains an open challenge. One approach to utilize lignin is its chemical deconstruction into mixtures of monomeric phenolic compounds followed by biological funneling into a single product. Novosphingobium aromaticivorans DSM12444 has been previously engineered to produce 2-pyrone-4,6-dicarboxylic acid (PDC) from depolymerized lignin by simultaneously metabolizing multiple aromatics through convergent routes involving the intermediates 3-methoxygallic acid (3-MGA) and protocatechuic acid (PCA). We investigated enzymes predicted to be responsible for O-demethylation and oxidative aromatic ring opening, two critical reactions involved in the metabolism of phenolics compounds by N. aromaticivorans The results showed the involvement of DesA in O-demethylation of syringic and vanillic acids, LigM in O-demethylation of vanillic acid and 3-MGA, and a new O-demethylase, DmtS, in the conversion of 3-MGA into gallic acid (GA). In addition, we found that LigAB was the main aromatic ring opening dioxygenase involved in 3-MGA, PCA, and GA metabolism, and that a previously uncharacterized dioxygenase, LigAB2, had high activity with GA. Our results indicate a metabolic route not previously identified in N. aromaticivorans that involves O-demethylation of 3-MGA to GA. We predict this pathway channels ∼15% of the carbon flow from syringic acid, with the rest following ring opening of 3-MGA. The new knowledge obtained in this study allowed for the creation of an improved engineered strain for the funneling of aromatic compounds that exhibits stoichiometric conversion of syringic acid into PDC.IMPORTANCE For lignocellulosic biorefineries to effectively contribute to reduction of fossil fuel use, they need to become efficient at producing chemicals from all major components of plant biomass. Making products from lignin will require engineering microorganisms to funnel multiple phenolic compounds to the chemicals of interest, and N. aromaticivorans is a promising chassis for this technology. The ability of N. aromaticivorans to efficiently and simultaneously degrade many phenolic compounds may be linked to having functionally redundant aromatic degradation pathways and enzymes with broad substrate specificity. A detailed knowledge of aromatic degradation pathways is thus essential to identify genetic engineering targets to maximize product yields. Furthermore, knowledge of enzyme substrate specificity is critical to redirect flow of carbon to desired pathways. This study described an uncharacterized pathway in N. aromaticivorans and the enzymes that participate in this pathway, allowing the engineering of an improved strain for production of PDC from lignin.

Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study.

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4-7 cycles, and/or every 2 months maintenance monotherapy for FL for 6-12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38·6% and were serious in 30·0%. AARs occurred in 48·6%, mostly (84·9%) at the injection site, with only 2·1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69·6%. After a median follow-up of 33·5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life.

Risk of Wnt/ß-catenin signalling pathway gene polymorphisms in primary Sjögren's syndrome.

OBJECTIVE: To explore genetic polymorphisms of the Wnt/ß-catenin signalling pathway in primary SS (PSS). METHODS: We included 98 patients with PSS and 165 healthy volunteers. Genomic DNA was extracted from peripheral blood samples. Through an open-array platform of low density, we genotyped 25 polymorphisms from 14 genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2, ADIPOQ and COL11A1) involved in the Wnt/ß-catenin signalling pathway. We compared the allelic and genotypic frequencies with Fisher's exact test and logistic regression analysis adjusted by age, gender and individual admixture, as well as bootstrap-resampling analysis. We assessed the gene-gene interaction by the multifactor dimensionality reduction method. RESULTS: We found a positive significant association with four polymorphisms: LRP5 rs606989, FRZB rs409238, GSK3B rs2037547 and ADIPOQ rs2241766. All of them conferred risk for PSS, being the highest among subjects carrying three to four risk alleles (P < 0.001). According to a multifactor dimensionality reduction analysis, the best models included the LRP5 (rs606989), FRZB (rs409238) and ADIPOQ (rs2241766) polymorphisms. CONCLUSION: LRP5, FRZB and ADIPOQ genes related in the Wnt/ß-catenin signalling pathway increased the risk of PSS. Further research is needed to establish their functional role in this clinical entity.

Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5.

The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands. GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation. In Gk5toku/toku mice, transcriptionally active SREBPs accumulated in the skin, but not in the liver; they were localized to the nucleus and led to elevated lipid synthesis and subsequent hair growth defects. Similar defective hair growth was observed in kinase-inactive GK5 mutant mice. Hair growth defects of homozygous toku mice were partially rescued by treatment with the HMG-CoA reductase inhibitor simvastatin. GK5 exists as part of a skin-specific regulatory mechanism for cholesterol biosynthesis, independent of cholesterol regulation elsewhere in the body.

Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.

BACKGROUND: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. OBJECTIVES: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. METHODS: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H1-antihistamines were studied. RESULTS: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H1-antihistamines were found. CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.

Relocation of Maternal-Fetal Medicine Specialists in the United States.

OBJECTIVE: To examine patterns in relocation of maternal-fetal medicine (MFM) specialists during the recent 10 years. STUDY DESIGN: This descriptive study analyzed the migration of MFM specialists between 2006 and 2016 based on county locations. Year-to-year comparisons of physicians in active clinical practice were performed. Demographic and county characteristics were gathered from three data resources. A multivariable logistic regression model was used to identify factors associated with relocation. RESULTS: An average of 7.4% (5.5-10.8%) of all 1,104 (1,103-1,115) MFM specialists moved per year. Approximately one in three (36%) relocated during the 10 years, usually once or twice. The likelihood of relocation was higher if the physician was younger, especially under 40 years compared with those aged 60 years and older (odds ratio [OR] = 2.08; 95% confidence interval [CI]: 1.36-3.19). No differences were noted based on gender and race/ethnicity. Physicians in independent group practices were more inclined to relocate, especially when compared with those in a solo or two-physician practice (OR = 0.38; 95% CI: 0.27-0.54). Relocations were primarily between urban counties (95.9%) and showed a significant regional pattern. CONCLUSION: Approximately one in three MFM specialists relocated in the past 10 years, mostly between urban counties and especially in independent group practices.

Determination of antibiotics in feedstuff samples by microemulsion electrokinetic chromatography using fullerene as additive.

A microemulsion electrokinetic chromatography method was developed for the simultaneous detection and quantification of ciprofloxacin, norfloxacin, sulfamethoxazole, tetracycline, and oxytetracycline in feedstuff samples. The BGE composition was optimized by applying a Taguchi parameter design and consisted of phosphate 30 mmol/L, Tween-80 0.01 mmol/L, and fullerene 3 µmol/L, and adjusted to pH 8.0; the addition of surfactant and fullerene modifies the mobility of the analytes improving their resolution. Theoretical studies showed π-π and van der Waals interactions between antibiotic molecules and fullerene used as a pseudostationary phase. Under optimal conditions, limits of detection ranged from 0.7 to 1.5 µg/g; the analytes were separated in less than 6 min. The methodology proposed is useful for controlling and monitoring antibiotic residues in feedstuff samples.

Vitamin D Deficiency is not Associated with Fatty Liver in a Mexican Population.

INTRODUCTION AND AIM: Association of vitamin D deficiency (VDD) with fatty liver (FL) disease is controversial. The purpose of this study was to analyze the association of VDD with FL. MATERIAL AND METHODS: Cross-sectional study. Data on cardiovascular risk factors, medications, alcohol intake, smoking, diet, and physical activity were obtained. Biochemical, anthropometric, and blood pressure variables were measured. The 25-hydroxyvitamin D (25(OH)D) was quantified through chemoluminescence. The presence of FL, defined as a liver/spleen attenuation index lower than 1.0, was identified through computed axial tomography (CAT). RESULTS: The study included 1,467 subjects (49.7% men) with a mean age of 53.3 ± 9.3 years and BMI of 28.3 ± 4.0 kg/m2. Only 11% had optimum values of vitamin D, and 25(OH)D concentration was lower in participants with FL. Multivariate logistic regression models, adjusted for age, gender, BMI, sampling season, glucose, total cholesterol, triglycerides, HOMA-IR, hs-CRP, ALT, AST, and elevated VAT, revealed an association between FL and vitamin D (VD) insufficiency (RM 1.61 [0.99-2.61]) and with VDD (RM 1.68 [1.02-2.77]); however, statistical significance was lost when including caloric consumption and physical activity in the model. CONCLUSIONS: In Mexican adults, deficient VD concentration and FL were not independently associated of caloric consumption and physical activity.

Bridged N-Heterocyclic/Mesoionic (NHC/MIC) Heterodicarbenes as Ligands for Transition Metal Complexes.

Following a copper catalyzed alkyne azide cycloaddition (CuAAC) and N-alkylation protocols, we report the preparation of a hybrid N-heterocyclic/mesoionic [NHC(H+)-MIC(H+)][2I]2- salt (1) in high yields. The treatment of salt 1 with Cu2O and KI yields a second hybrid NHC/MIC proligand featuring a tetraiodocuprate anion [NHC(H+)-MIC(H+)][Cu2I4]2- (2). Through selective deprotonation and metalation, both salts 1 and 2 can generate either the chelate heterodicarbene complexes (3) with the rare [NHC·(M)·MIC]+[MX2]- general formula (M = PdII, RhI) or NHC-anchored/pendent triazolium species (4) [NHC·(M)-MIC(H+)]. If the triazolium moiety of type 4 complexes is deprotonated with KHMDS in the presence of a second metal center, a series of heterobimetallic complexes of the type [NHC·(M)-MIC·(M')] (5) are achieved. Interestingly, the reaction of salt 2 with KHMDS yields the bimetallic copper heterodicarbene (6) which can be a useful transfer reagent for the preparation of type 3 complexes. A variety of synthetic routes for the preparation of complexes 3-5 and their full characterization in solution and in the solid state will be discussed.

Evaluation of CETP activity in vivo under non-steady-state conditions: influence of anacetrapib on HDL-TG flux.

Studies in lipoprotein kinetics almost exclusively rely on steady-state approaches to modeling. Herein, we have used a non-steady-state experimental design to examine the role of cholesteryl ester transfer protein (CETP) in mediating HDL-TG flux in vivo in rhesus macaques, and therefore, we developed an alternative strategy to model the data. Two isotopomers ([(2)H11] and [(13)C18]) of oleic acid were administered (orally and intravenously, respectively) to serve as precursors for labeling TGs in apoB-containing lipoproteins. The flux of a specific TG (52:2) from these donor lipoproteins to HDL was used as the measure of CETP activity; calculations are also presented to estimate total HDL-TG flux. Based on our data, we estimate that the peak total postprandial TG flux to HDL via CETP is ∼ 13 mg · h(-1) · kg(-1) and show that this transfer was inhibited by 97% following anacetrapib treatment. Collectively, these data demonstrate that HDL TG flux can be used as a measure of CETP activity in vivo. The fact that the donor lipoproteins can be labeled in situ using well-established stable isotope tracer techniques suggests ways to measure this activity for native lipoproteins in free-living subjects under any physiological conditions.

Octadecyl-viologen Photooxidation in Surface Films: Macroscopic Contraction of Langmuir Monolayer by UV Irradiation.

The effects of UV radiation on a viologen derivative, octadecylviologen (OV), in Langmuir monolayers at the air-aqueous solution interface and in Langmuir-Blodgett (LB) films have been investigated. Langmuir monolayers suffer a sharp contraction after UV irradiation, clearly visible by the drop in surface pressure or the loss of surface area observed in the surface pressure-area isotherms. The UV-vis reflection measurements reveal a deep change in the OV monolayer caused by a photochemical reaction, which suggests the pyridones formation as photoreaction products. LB films (Z type), before and after being irradiated with UV light, have been studied by using UV-vis absorption and infrared and X-ray photoelectron spectroscopy. The results confirm that after the photodegradation of the viologen films, the presence of oxygen results in the appearance of pyridones as reaction products. This article demonstrates that, in the absence of catalysts, the photooxidation of viologen surface films occurs only under a particular molecular organization imposed by the air-water interface.

Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbits.

Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5% cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis.

Effects of an antioxidant beverage on biomarkers of oxidative stress in Alzheimer's patients.

PURPOSE: The purpose of the study was to test whether daily consumption of a beverage with high antioxidant power, combining extracts of green tea and apple over a period of 8 months, would affect blood and urinary concentrations of biomarkers of oxidative stress in Alzheimer's patients. METHODS: The study included 100 subjects, 48 of them were Alzheimer's patients, aged 76.5 ± 3.5 years, and 52 were control subjects, aged 79 ± 4 years, without dementia. Three blood and urine samples were taken from each participant, the first (T i) before starting the antioxidant or placebo beverage intake, the second (T m) 4 months after the antioxidant or placebo beverage intake and the third (T f) 8 months after the antioxidant or placebo beverage intake, and concentrations of biomarkers of oxidative stress were measured on serum, lysed erythrocytes or urine by UV-Vis spectrophotometry or by competitive in vitro enzyme-linked immunosorbent assay, according to the parameter analyzed. RESULTS: The administration of the antioxidant beverage to the Alzheimer's patients prevented the decrease in total antioxidant status in the moderate phase of the disease (T i = 1.40 ± 0.10 mmol/L vs T f = 1.20 ± 0.08 mmol/L), increased values of glutathione peroxidase and superoxide dismutase in initial (165 and 24 % respectively) and moderate phase (75 and 85 % respectively), and prevented the increase in protein carbonyls in moderate phase (T i = 0.17 ± 0.07 nmol/mg protein vs T f = 0.21 ± 0.06 nmol/mg protein), with a significant decrease in protein carbonyls since the fourth month of the intake in initial phase (T m = 0.21 ± 0.06 nmol/mg protein vs T f = 0.11 ± 0.05 nmol/mg protein). CONCLUSION: Our results suggest that antioxidant beverage could be used as a natural complementary therapy for alleviate or decrease the oxidative stress effects in the stages of Alzheimer's disease.