The application of a profluorescent nitroxide probe to detect reactive oxygen species derived from combustion-generated particulate matter

Particulate pollution has been widely recognised as an important risk factor to human health. In addition to increases in respiratory and cardiovascular morbidity associated with exposure to particulate matter (PM), WHO estimates that urban PM causes 0.8 million premature deaths globally and that 1.5 million people die prematurely from exposure to indoor smoke generated from the combustion of solid fuels. Despite the availability of a huge body of research, the underlying toxicological mechanisms by which particles induce adverse health effects are not yet entirely understood. Oxidative stress caused by generation of free radicals and related reactive oxygen species (ROS) at the sites of deposition has been proposed as a mechanism for many of the adverse health outcomes associated with exposure to PM. In addition to particle-induced generation of ROS in lung tissue cells, several recent studies have shown that particles may also contain ROS. As such, they present a direct cause of oxidative stress and related adverse health effects. Cellular responses to oxidative stress have been widely investigated using various cell exposure assays. However, for a rapid screening of the oxidative potential of PM, less time-consuming and less expensive, cell-free assays are needed. The main aim of this research project was to investigate the application of a novel profluorescent nitroxide probe, synthesised at QUT, as a rapid screening assay in assessing the oxidative potential of PM. Considering that this was the first time that a profluorescent nitroxide probe was applied in investigating the oxidative stress potential of PM, the proof of concept regarding the detection of PM–derived ROS by using such probes needed to be demonstrated and a sampling methodology needed to be developed. Sampling through an impinger containing profluorescent nitroxide solution was chosen as a means of particle collection as it allowed particles to react with the profluorescent nitroxide probe during sampling, avoiding in that way any possible chemical changes resulting from delays between the sampling and the analysis of the PM. Among several profluorescent nitroxide probes available at QUT, bis(phenylethynyl)anthracene-nitroxide (BPEAnit) was found to be the most suitable probe, mainly due to relatively long excitation and emission wavelengths (λex= 430 nm; λem= 485 and 513 nm). These wavelengths are long enough to avoid overlap with the background fluorescence coming from light absorbing compounds which may be present in PM (e.g. polycyclic aromatic hydrocarbons and their derivatives). Given that combustion, in general, is one of the major sources of ambient PM, this project aimed at getting an insight into the oxidative stress potential of combustion-generated PM, namely cigarette smoke, diesel exhaust and wood smoke PM. During the course of this research project, it was demonstrated that the BPEAnit probe based assay is sufficiently sensitive and robust enough to be applied as a rapid screening test for PM-derived ROS detection. Considering that for all three aerosol sources (i.e. cigarette smoke, diesel exhaust and wood smoke) the same assay was applied, the results presented in this thesis allow direct comparison of the oxidative potential measured for all three sources of PM. In summary, it was found that there was a substantial difference between the amounts of ROS per unit of PM mass (ROS concentration) for particles emitted by different combustion sources. For example, particles from cigarette smoke were found to have up to 80 times less ROS per unit of mass than particles produced during logwood combustion. For both diesel and wood combustion it has been demonstrated that the type of fuel significantly affects the oxidative potential of the particles emitted. Similarly, the operating conditions of the combustion source were also found to affect the oxidative potential of particulate emissions. Moreover, this project has demonstrated a strong link between semivolatile (i.e. organic) species and ROS and therefore, clearly highlights the importance of semivolatile species in particle-induced toxicity.

Leptospirosis and Leptospires - The silent assassins

Leptospirosis is one of the most common yet under reported zoonoses. Leptospires, the etiological agents of leptospirosis are ubiquitous pathogens, with a world-wide distribution, causing a spectrum of disease ranging from a mild influenza-like illness to Weil’s disease, which manifests itself in multi-organ failure. The following chapter reports on the epidemiology and transmission of the disease in humans and animals. The chapter will also delineate the symptoms observed in humans and animals and in concluding outline unresolved and evolving issues for microbiologists, epidemiologists and public health officials.

MOHO EN ESPACIOS INTERIORES

This paper written in Spanish gives hints on what to do to control mold after the flooding in October 2015 in South Carolina. Topics include: presence of mold after a flood, signs of mold, people at greatest risk for health effects from mold, possible health effects of mold exposure and cleaning wet or moldy Items after a flood. It also gives web sites for additional information and resources.

Analysis of temperature time-series: embedding dynamics into the MDS method

Global warming and the associated climate changes are being the subject of intensive research due to their major impact on social, economic and health aspects of the human life. Surface temperature time-series characterise Earth as a slow dynamics spatiotemporal system, evidencing long memory behaviour, typical of fractional order systems. Such phenomena are difficult to model and analyse, demanding for alternative approaches. This paper studies the complex correlations between global temperature time-series using the Multidimensional scaling (MDS) approach. MDS provides a graphical representation of the pattern of climatic similarities between regions around the globe. The similarities are quantified through two mathematical indices that correlate the monthly average temperatures observed in meteorological stations, over a given period of time. Furthermore, time dynamics is analysed by performing the MDS analysis over slices sampling the time series. MDS generates maps describing the stations’ locus in the perspective that, if they are perceived to be similar to each other, then they are placed on the map forming clusters. We show that MDS provides an intuitive and useful visual representation of the complex relationships that are present among temperature time-series, which are not perceived on traditional geographic maps. Moreover, MDS avoids sensitivity to the irregular distribution density of the meteorological stations.

Attenuation of skeletal muscle FFA-induced insulin resistance by the polyphenol resveratrol. Elucidation of the mechanisms involved

Excess plasma free fatty acids (FFA) are correlated with insulin resistance and are a risk factor for the development of type 2 diabetes. In this study we examined the effect of the polyphenol resveratrol on FF A-induced insulin resistance in skeletal muscle cells and the mechanisms involved. Incubation of L6 myotubes with the FF A palmitate significantly decreased the insulin-stimulated glucqse uptake. Importantly, the effect of palmitate was ameliorated by resveratrol. Palmitate significantly increased serine phosphorylation of IRS..; 1 and reduced insulin-stimulated Akt phosphorylation, an effect that was abolished by resveratrol. We then investigated the effect of palmitate and resveratrol on the expression and phosphorylation of JNK, mTOR, p70-S6K, and AMPK kinases. The results demonstrated that our treatments had no effect on the expression of these proteins. However, palmitate increased the phosphorylation of mTOR and p70- S6K, whereas resveratrol abolished this effect and increased the phosphorylation of AMPK. Furthermore, all effects of resveratrol were abolished with sirtuin inhibitors, sirtinol and nicotinamide. These results indicate that resveratrol ameliorated FF A-induced insulin resistance by regulating mTOR and p70-S6K phosphorylation in skeletal muscle cells, through a mechanism involving sirtuins.

Relative importance of body composition, osteoporosis- related behaviours and socioeconomic status on bone SOS in adolescent females

The purpose of this study was to examine the associations between bone speed of sound (SOS) and body composition, osteoporosis-related health behaviours, and socioeconomic status (SES) in adolescent females. A total of 442 adolescent females in grades 9-11 participated. Anthropometric measures of height, body mass, and percent body fat were taken, and osteo-protective behaviours such as oral contraceptive use (OC), physical activity and daily calcium intake were evaluated using self-report questionnaires. Bone SOS was measured by transaxial quantitative ultrasound (QUS) at the distal radius and mid-tibia. The results suggest that fat mass is a significant negative predictor of tibial SOS, while lean mass is positively associated with radial SOS scores and calcium intake was positively associated with tibial SOS scores (p

The relationship between body mass index and breast cancer recurrence/progression and breast cancer-specific death

The aim of this study was to describe the nonlinear association between body mass index (BMI) and breast cancer outcomes and to determine whether BMI improves prediction of outcomes. A cohort of906 breast cancer patients diagnosed at Henry Ford Health System, Detroit (1985-1990) were studied. The median follow-up was 10 years. Multivariate logistic regression was used to model breast cancer recurrence/progression and breast cancer-specific death. Restricted cubic splines were used to model nonlinear effects. Receiver operator characteristic areas under the curves (ROC AUC) were used to evaluate prediction. BMI was nonlinearly associated with recurrence/progression and death (p= 0.0230 and 0.0101). Probability of outcomes increased with increase or decrease ofBMI away from 25. BMI splines were suggestive of improved prediction of death. The ROC AUCs for nested models with and without BMI were 0.8424 and 0.8331 (p= 0.08). I f causally associated, modifying patients BMI towards 25 may improve outcomes.

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Efectos fisiológicos de la termorregulación en trabajadores expuestos a altas temperaturas en una Siderúrgica en Colombia.

La exposición a altas temperaturas en ambientes laborales conlleva a cambios fisiológicos que se manifiestan como mecanismos de compensación a la alteración del equilibrio homeostático corporal. El propósito del presente estudio fue determinar los cambios y el comportamiento de variables fisiológicas a través de frecuencia cardiaca, densidad urinaria, temperatura corporal y tasa de sudoración, en dos escenarios con condiciones térmicas ambientales diferentes definidas por la exposición (grupo expuesto y no expuesto). Adicional, en dos áreas de trabajo diferentes correspondientes al proceso de fundición del acero, una de ellas, Horno electrico donde se hace la fusión de la chatarra y demás materias primas, obteniendo así el acero liquido, el cual se vuelca en el Horno Cuchara y en este, libre ya de escoria se realiza el afino y ajuste definitivo de la composición química del acero. Objetivos: Identificar la relación de las respuestas fisiológicas a carga física y térmica, comparar las respuestas funcionales registradas en el grupo expuestos y no expuestos y contribuir a la introducción de nuevos indicadores para evaluar carga e intensidad de trabajo con fines de normalización ergonómica. Método: Investigación experimental en una muestra de 30 trabajadores evaluados en dos condiciones ambientales diferentes. La temperatura oral se registró al inicio de la jornada y con intervalos de toma de 3 horas. La frecuencia cardiaca (HR) se registró durante las 8 horas de trabajo continuas con pulsometría. Igualmente, se estimó la sudoración por pérdida de masa corporal entre el inicio y el final de la jornada laboral teniendo en cuenta ingestas y perdidas. El procesamiento estadístico se realizó con el programa SPSS v. 20.0, calculándose medidas de tendencia central y dispersión, prueba de wilconxon para las variables dependientes y correlación para identificar asociaciones. Para todos los cálculos se asumió p <0,05. Resultados: No se observaron diferencias significativas frente a la variación de la frecuencia cardiaca (media y máxima), la tasa de sudoración y la densidad urinaria. A pesar de que no hubo diferencias significativas en la variación de la temperatura corporal en horno cuchara, si se observó una diferencia significativa en el horno eléctrico Conclusión: Aunque no se encontraron diferencias estadísticamente significativas en la mayoría de las variables, es un hecho que la exposición a temperaturas elevadas extremas tiene un impacto en el comportamiento fisiológico del organismo. Futuros estudios deben considerar la posibilidad de estandarizar protocolos que permitan la exposición térmica basada en el perfil particular de cada trabajador.

Dietary modulation of the human colonic microbiota: updating the concept of prebiotics

Prebiotics are non-digestible (by the host) food ingredients that have a beneficial effect through their selective metabolism in the intestinal tract. Key to this is the specificity of microbial changes. The present paper reviews the concept in terms of three criteria: (a) resistance to gastric acidity, hydrolysis by mammalian enzymes and gastrointestinal absorption; (b) fermentation by intestinal microflora; (c) selective stimulation of the growth and/or activity of intestinal bacteria associated with health and wellbeing. The conclusion is that prebiotics that currently fulfil these three criteria are fructo-oligosaccharides, galacto-oligosaccharides and lactulose, although promise does exist with several other dietary carbohydrates. Given the range of food vehicles that may be fortified by prebiotics, their ability to confer positive microflora changes and the health aspects that may accrue, it is important that robust technologies to assay functionality are used. This would include a molecular-based approach to determine flora changes. The future use of prebiotics may allow species-level changes in the microbiota, an extrapolation into genera other than the bifidobacteria and lactobacilli, and allow preferential use in disease-prone areas of the body.

Performance evaluation of ventilation radiators

A ventilation radiator is a combined ventilation and heat emission unit currently of interest due to its potential for increasing energy efficiency in exhaust ventilated buildings with warm water heating. This paper presents results of performance tests of several ventilation radiator models conducted under controlled laboratory conditions.   The purpose of the study was to validate results achieved by Computational Fluid Dynamics (CFD) in an earlier study and indentify possible improvements in the performance of such systems. The main focus was on heat transfer from internal convection fins, but comfort and health aspects related to ventilation rates and air temperatures were also considered.   The general results from the CFD simulations were confirmed; the heat output of ventilation radiators may be improved by at least 20 % without sacrificing ventilation efficiency or thermal comfort.   Improved thermal efficiency of ventilation radiators allows a lower supply water temperature and energy savings both for heating up and distribution of warm water in heat pumps or district heating systems. A secondary benefit is that a high ventilation rate can be maintained all year around without risk for cold draught.

What is all the fuss about trans fatty acids?

The level of trans-monounsaturated fatty acids in manufactured foods is largely unknown, however the survey showed the levels varied from 0.5% to 22.5% of total fatty acids in 55 foods tested. This survey data shows that these fatty acids raise blood cholesterol levels even more than saturated fat, which made labelling of foods for trans fatty acids mandatory.