Smoking cessation and the incidence of pre-diabetes and type 2 diabetes: a cohort study.

AIMS: Smoking cessation has been suggested to increase the short-term risk of type 2 diabetes mellitus (T2DM). This study aimed at assessing the association between smoking cessation and incidence of T2DM and impaired fasting glucose (IFG). METHODS: Data from participants in the CoLaus study, Switzerland, aged 35-75 at baseline and followed for 5.5years were used. Participants were classified as smokers, recent (≤5years), long-term (>5years) quitters, and non-smokers at baseline. Outcomes were IFG (fasting serum glucose (FSG) 5.6-6.99mmol/l) and T2DM (FSG ≥7.0mmol/l and/or treatment) at follow up. RESULTS: 3,166 participants (63% women) had normal baseline FSG, of whom 26.7% were smokers, 6.5% recent quitters, and 23.5% long-term quitters. During follow-up 1,311 participants (41.4%) developed IFG (33.6% women, 54.7% men) and 47 (1.5%) developed T2DM (1.1% women, 2.1% men). Former smokers did not have statistically significant increased odds of IFG compared with smokers after adjustment for age, education, physical activity, hypercholesterolemia, hypertension and alcohol intake, with OR of 1.29 [95% confidence interval 0.94-1.76] for recent quitters and 1.03 [0.84-1.27] for long-term quitters. Former smokers did not have significant increased odds of T2DM compared with smokers with multivariable-adjusted OR of 1.53 [0.58-4.00] for recent quitters and 0.64 [0.27-1.48] for long-term quitters. Adjustment for body-mass index and waist circumference attenuated the association between recent quitting and IFG (OR 1.07 [0.78-1.48]) and T2DM (OR 1.28 [0.48-3.40]. CONCLUSION: In this middle-aged population, smoking cessation was not associated with an increased risk of IFG or T2DM.

Stability of nanoparticle agglomerates under mechanical stress and its effects on their release into the air

L'exposition professionnelle aux nanomatériaux manufacturés dans l'air présente des risques potentiels pour la santé des travailleurs dans les secteurs de la nanotechnologie. Il est important de comprendre les scénarios de libération des aérosols de nanoparticules dans les processus et les activités associées à l'exposition humaine. Les mécanismes de libération, y compris les taux de libération et les propriétés physico-chimiques des nanoparticules, déterminent leurs comportements de transport ainsi que les effets biologiques néfastes. La distribution de taille des particules d'aérosols est l'un des paramètres les plus importants dans ces processus. La stabilité mécanique d'agglomérats de nanoparticules affecte leurs distributions de tailles. Les potentiels de désagglomération de ces agglomérats déterminent les possibilités de leur déformation sous énergies externes. Cela rend les changements possibles dans leur distribution de taille et de la concentration en nombre qui vont finalement modifier leurs risques d'exposition. Les conditions environnementales, telles que l'humidité relative, peuvent influencer les processus de désagglomération par l'adhérence de condensation capillaire de l'humidité. L'objectif général de cette thèse était d'évaluer les scénarios de libération des nanomatériaux manufacturés des processus et activités sur le lieu de travail. Les sous-objectifs étaient les suivants: 1. Etudier les potentiels de désagglomération des nanoparticules dans des conditions environnementales variées. 2. Etudier la libération des nano-objets à partir de nanocomposites polymères; 3. Evaluer la libération de nanoparticules sur le lieu de travail dans des situations concrètes. Nous avons comparé différents systèmes de laboratoire qui présentaient différents niveau d'énergie dans l'aérosolisation des poudres. Des nanopoudres de TiO2 avec des hydrophilicités de surface distinctes ont été testées. Un spectromètre à mobilité électrique (SMPS), un spectromètre à mobilité aérodynamique (APS) et un spectromètre optique (OPC) ont été utilisés pour mesurer la concentration de particules et la distribution de taille des particules. La microscopie électronique à transmission (TEM) a été utilisée pour l'analyse morphologique d'échantillons de particules dans l'air. Les propriétés des aérosols (distribution de taille et concentration en nombre) étaient différentes suivant la méthode employée. Les vitesses des flux d'air d'aérosolisation ont été utilisées pour estimer le niveau d'énergie dans ces systèmes, et il a été montré que les tailles modales des particules étaient inversement proportionnelles à la vitesse appliquée. En général, les particules hydrophiles ont des diamètres plus grands et des nombres inférieurs à ceux des particules hydrophobes. Toutefois, cela dépend aussi des méthodes utilisées. La vitesse de l'air peut donc être un paramètre efficace pour le classement de l'énergie des procédés pour des systèmes d'aérosolisation similaires. Nous avons développé un système laboratoire pour tester les potentiels de désagglomération des nanoparticules dans l'air en utilisant des orifices critiques et un humidificateur. Sa performance a été comparée à un système similaire dans un institut partenaire. Une variété de nanopoudres différentes a été testée. Le niveau d'énergie appliquée et l'humidité ont été modifiés. Le SMPS et l'OPC ont été utilisés pour mesurer la concentration de particules et la distribution de la taille. Un TEM a été utilisé pour l'analyse morphologique d'échantillons de particules dans l'air. Le diamètre moyen des particules a diminué et la concentration en nombre s'est accrue lorsque des énergies externes ont été appliquées. Le nombre de particules inférieures à 100 nm a été augmenté, et celui au-dessus de 350 nm réduits. Les conditions humides ont faits exactement le contraire, en particulier pour les petites particules. En outre, ils ont réduits les effets de la différence de pression due à l'orifice. Les résultats suggèrent que la désagglomération d'agglomérats de nanoparticules dans l'air est possible dans la gamme d'énergie appliquée. Cependant, l'atmosphère humide peut favoriser leur agglomération et améliorer leurs stabilités en réduisant la libération de nanoparticules dans l'environnement. Nous proposons d'utiliser notre système pour le test de routine des potentiels de désagglomération des nanomatériaux manufacturés et de les classer. Un tel classement faciliterait la priorisation de l'exposition et du risque encouru en fonction du niveau d'ENM. Un système de perçage automatique et un système de sciage manuel ont été développés pour étudier la libération de nanoparticules à partir de différents types de nanocomposites. La vitesse de perçage et taille de la mèche ont été modifiées dans les expériences. La distribution de taille des particules et leur concentration en nombre ont été mesurées par un SMPS et un miniature diffusion size classifier (DISCmini). Les distributions de nanoparticules dans les composites et les particules libérées ont été analysés par un TEM et un microscope électronique à balayage (SEM). Les tests de perçage ont libérés un plus grand nombre de particules que le sciage. Des vitesses de perçage plus rapide et les mèches plus grandes ont augmentés la génération de particules. Les charges de nanoparticules manufacturées dans les composites ne modifient pas leurs comportements de libération dans les expériences de perçage. Toutefois, le sciage différencie les niveaux de libération entre les composites et les échantillons blancs. De plus, les vapeurs de polymères ont été générées par la chaleur de sciage. La plupart des particules libérées sont des polymères contenant des nanoparticules ou sur leurs surface. Les résultats ont souligné l'importance du type de processus et paramètres pour déterminer la libération de nanoparticules de composites. Les émissions secondaires telles que les fumées polymères appellent à la nécessité d'évaluations de l'exposition et de risque pour de tels scénarios. Une revue systématique de la littérature sur le sujet de libérations de nanoparticules dans l'air dans les secteurs industriels et laboratoires de recherche a été effectuée. Des stratégies de recherche des informations pertinentes et de stockage ont été développées. Les mécanismes de libération, tels que la taille de particules d'aérosol et de leur concentration en nombre, ont été comparés pour différentes activités. La disponibilité de l'information contextuelle qui est pertinente pour l'estimation de l'exposition humaine a été évaluée. Il a été constaté que les données relatives à l'exposition ne sont pas toujours disponibles dans la littérature actuelle. Les propriétés des aérosols libérés semblent dépendre de la nature des activités. Des procédés à haute énergie ont tendance à générer des plus hauts niveaux de concentrations de particules dans les gammes de plus petite taille. Les résultats peuvent être utiles pour déterminer la priorité des procédés industriels pour l'évaluation les risques associés dans une approche à plusieurs niveaux. Pour l'évaluation de l'exposition, la disponibilité de l'information peut être améliorée par le développement d'une meilleure méthode de communication des données.

Cyclosporine A kinetics in brain cell cultures and its potential of crossing the blood-brain barrier.

There is an increasing need to develop improved systems for predicting the safety of xenobiotics. However, to move beyond hazard identification the available concentration of the test compounds needs to be incorporated. In this study cyclosporine A (CsA) was used as a model compound to assess the kinetic profiles in two rodent brain cell cultures after single and repeated exposures. CsA induced-cyclophilin B (Cyp-B) secretion was also determined as CsA-specific pharmacodynamic endpoint. Since CsA is a potent p-glycoprotein substrate, the ability of this compound to cross the blood-brain barrier (BBB) was also investigated using an in vitro bovine model with repeated exposures up to 14days. Finally, CsA uptake mechanisms were studied using a parallel artificial membrane assay (PAMPA) in combination with a Caco-2 model. Kinetic results indicate a low intracellular CsA uptake, with no marked bioaccumulation or biotransformation. In addition, only low CsA amounts crossed the BBB. PAMPA and Caco-2 experiments revealed that CsA is mostly trapped to lipophilic compartments and exits the cell apically via active transport. Thus, although CsA is unlikely to enter the brain at cytotoxic concentrations, it may cause alterations in electrical activity and is likely to increase the CNS concentration of other compounds by occupying the BBBs extrusion capacity. Such an integrated testing system, incorporating BBB, brain culture models and kinetics could be applied for assessing neurotoxicity potential of compounds.

Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure.

Urinary di-(2-ethylhexyl) phthalate metabolites for detecting transfusion of autologous blood stored in plasticizer-free bags.

BACKGROUND: Autologous blood transfusion (ABT) efficiently increases sport performance and is the most challenging doping method to detect. Current methods for detecting this practice center on the plasticizer di(2-ethlyhexyl) phthalate (DEHP), which enters the stored blood from blood bags. Quantification of this plasticizer and its metabolites in urine can detect the transfusion of autologous blood stored in these bags. However, DEHP-free blood bags are available on the market, including n-butyryl-tri-(n-hexyl)-citrate (BTHC) blood bags. Athletes may shift to using such bags to avoid the detection of urinary DEHP metabolites. STUDY DESIGN AND METHODS: A clinical randomized double-blinded two-phase study was conducted of healthy male volunteers who underwent ABT using DEHP-containing or BTHC blood bags. All subjects received a saline injection for the control phase and a blood donation followed by ABT 36 days later. Kinetic excretion of five urinary DEHP metabolites was quantified with liquid chromatography coupled with tandem mass spectrometry. RESULTS: Surprisingly, considerable levels of urinary DEHP metabolites were observed up to 1 day after blood transfusion with BTHC blood bags. The long-term metabolites mono-(2-ethyl-5-carboxypentyl) phthalate and mono-(2-carboxymethylhexyl) phthalate were the most sensitive biomarkers to detect ABT with BTHC blood bags. Levels of DEHP were high in BTHC bags (6.6%), the tubing in the transfusion kit (25.2%), and the white blood cell filter (22.3%). CONCLUSIONS: The BTHC bag contained DEHP, despite being labeled DEHP-free. Urinary DEHP metabolite measurement is a cost-effective way to detect ABT in the antidoping field even when BTHC bags are used for blood storage.

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.

BACKGROUND: While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. METHODS: 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). RESULTS: 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. CONCLUSIONS: The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies.

Validation of French and German versions of a Perceived Neighborhood Social Cohesion questionnaire among young Swiss males, and its relationship with substance use

This study main purpose was the validation of both French and German versions of a Perceived Neighborhood Social Cohesion Questionnaire. The sample group comprised 5065 Swiss men from the "Cohort Study on Substance Use Risk Factors." Multigroup Confirmatory factor analysis showed that a three-factor model fits the data well, which substantiates the generalizability of Perceived Neighborhood Social Cohesion Questionnaire factor structure, regardless of the language. The Perceived Neighborhood Social Cohesion Questionnaire demonstrated excellent homogeneity (α = 95) and split-half reliability (r = .96). The Perceived Neighborhood Social Cohesion Questionnaire was sensitive to community size and participants' financial situation, confirming that it also measures real social conditions. Finally, weak but frequent correlations between Perceived Neighborhood Social Cohesion Questionnaire and alcohol, cigarette, and cannabis dependence were measured.

Rotational assessment of distal femur and its relevance in total knee arthroplasty: analysis by magnetic resonance imaging

AbstractObjective:To define the distal femur rotation pattern in a Brazilian population, correlating such pattern with the one suggested by the arthroplasty instruments, and analyzing the variability of each anatomic parameter.Materials and Methods:A series of 101 magnetic resonance imaging studies were evaluated in the period between April and June 2012. The epidemiological data collection was performed with the aid of the institution's computed imaging system, and the sample included 52 male and 49 female patients. The measurements were made in the axial plane, with subsequent correlation and triangulation with the other plans. The posterior condylar line was used as a reference for angle measurements. Subsequently, the anatomical and surgical transepicondylar axes and the anteroposterior trochlear line were specified. The angles between the reference line and the studied lines were calculated with the aid of the institution's software.Results:The mean angle between the anatomical transepicondylar axis and the posterior condylar line was found to be 6.89°, ranging from 0.25° to 12°. For the surgical transepicondylar axis, the mean value was 2.89°, ranging from –2.23° (internal rotation) to 7.86°, and for the axis perpendicular to the anteroposterior trochlear line, the mean value was 4.77°, ranging from –2.09° to 12.2°.Conclusion:The anatomical transepicondylar angle showed mean values corresponding to the measurement observed in the Caucasian population. The utilized instruments are appropriate, but no anatomical parameter proved to be steady enough to be used in isolation.

Undressing of Waddlia chondrophila to enrich its outer membrane proteins to develop a new species-specific ELISA.

Waddlia chondrophila, an obligate intracellular bacterium of the Chlamydiales order, is considered as an agent of bovine abortion and a likely cause of miscarriage in humans. Its role in respiratory diseases was questioned after the detection of its DNA in clinical samples taken from patients suffering from pneumonia or bronchiolitis. To better define the role of Waddlia in both miscarriage and pneumonia, a tool allowing large-scale serological investigations of Waddlia seropositivity is needed. Therefore, enriched outer membrane proteins of W. chondrophila were used as antigens to develop a specific ELISA. After thorough analytical optimization, the ELISA was validated by comparison with micro-immunofluorescence and it showed a sensitivity above 85% with 100% specificity. The ELISA was subsequently applied to human sera to specify the role of W. chondrophila in pneumonia. Overall, 3.6% of children showed antibody reactivity against W. chondrophila but no significant difference was observed between children with and without pneumonia. Proteomic analyses were then performed using mass spectrometry, highlighting members of the outer membrane protein family as the dominant proteins. The major Waddlia putative immunogenic proteins were identified by immunoblot using positive and negative human sera. The new ELISA represents an efficient tool with high throughput applications. Although no association with pneumonia and Waddlia seropositivity was observed, this ELISA could be used to specify the role of W. chondrophila in miscarriage and in other diseases.

Solitary pulmonary nodule and 18F-FDG PET/CT. Part 2: accuracy, cost-effectiveness, and current recommendations

Abstract A solitary pulmonary nodule is a common, often incidental, radiographic finding. The investigation and differential diagnosis of solitary pulmonary nodules remain complex, because there are overlaps between the characteristics of benign and malignant processes. There are currently many strategies for evaluating solitary pulmonary nodules. The main objective is to identify benign lesions, in order to avoid exposing patients to the risks of invasive methods, and to detect cases of lung cancer accurately, in order to avoid delaying potentially curative treatment. The focus of this study was to review the evaluation of solitary pulmonary nodules, to discuss the current role of 18F-fluorodeoxyglucose positron-emission tomography, addressing its accuracy and cost-effectiveness, and to detail the current recommendations for the examination in this scenario.

A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX.

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. © 2015 American Society for Bone and Mineral Research.

Estudo da adsorção/dessorção do ácido 2,4 diclorofenoxiacético (2,4d) em solo na ausência e presença de matéria orgânica

The herbicides are being used in huge quantities for various porpouses. Once the herbicide finds its way into the environment, a major part of it comes in contact with soil. Humic substances are major organic constituents of soil. These substances may interact with herbicides in different modes and adsorption is probably the most important one. Adsorption will control the quantity of herbicide in the soil solution, and determines its persistence, leaching, mobility and bioavailability. In this work we studied the interaction between the herbicide 2,4D and soil in the presence and absence of organic matter. The methodology utilized for the determination of 2,4D was gas chromatography with eletron capture detector. The behavior of 2,4D was evaluated through Freundlich isotherms. It was verified that the herbicide 2,4D has a large adsorption in the humic acid .

Síntese e atividade fitotóxica de 2-fenil-6,7-exo-isopropilidenodioxi-8-oxabiciclo [3.2.1]oct-2-eno

The [3+4] cycloaddition between furan and the oxyallyl cation generated from 1-bromo-1-phenylpropan-2-one (4), resulted in the formation of 2-phenyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (5) in 30% yield. This compound was further converted into 2-phenyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]oct-2-ene (13) in 35.4% yield. The selective effect of compound (13) and its isomer 3-phenyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]oct -2-ene (1a) on the radicle growth of Sorghum bicolor L. (sorghum) and Cucumis sativus L. (cucumber) were evaluated. For both plants, compound 13 showed to be more potent than its isomer 1a.

Analysis of a Plant Complex Resistance Gene Locus Underlying Immune-Related Hybrid Incompatibility and Its Occurrence in Nature

Mechanisms underlying speciation in plants include detrimental (incompatible) genetic interactions between parental alleles that incur a fitness cost in hybrids. We reported on recessive hybrid incompatibility between an Arabidopsis thaliana strain from Poland, Landsberg erecta (Ler), and many Central Asian A. thaliana strains. The incompatible interaction is determined by a polymorphic cluster of Toll/interleukin-1 receptor-nucleotide binding-leucine rich repeat (TNL) RPP1 (Recognition of Peronospora parasitica1)-like genes in Ler and alleles of the receptor-like kinase Strubbelig Receptor Family 3 (SRF3) in Central Asian strains Kas-2 or Kond, causing temperature-dependent autoimmunity and loss of growth and reproductive fitness. Here, we genetically dissected the RPP1-like Ler locus to determine contributions of individual RPP1-like Ler (R1R8) genes to the incompatibility. In a neutral background, expression of most RPP1-like Ler genes, except R3, has no effect on growth or pathogen resistance. Incompatibility involves increased R3 expression and engineered R3 overexpression in a neutral background induces dwarfism and sterility. However, no individual RPP1-like Ler gene is sufficient for incompatibility between Ler and Kas-2 or Kond, suggesting that co-action of at least two RPP1-like members underlies this epistatic interaction. We find that the RPP1-like Ler haplotype is frequent and occurs with other Ler RPP1-like alleles in a local population in Gorzów Wielkopolski (Poland). Only Gorzów individuals carrying the RPP1-like Ler haplotype are incompatible with Kas-2 and Kond, whereas other RPP1-like alleles in the population are compatible. Therefore, the RPP1-like Ler haplotype has been maintained in genetically different individuals at a single site, allowing exploration of forces shaping the evolution of RPP1-like genes at local and regional population scales.