LUNG CANCER IN NEPAL: THE ROLE OF TRADITIONAL TOBACCO PRODUCTS AND COMBUSTION RELATED HOUSEHOLD AIR POLLUTION

The burden of chronic diseases such as cancer is increasing in low and middle income countries around the globe. Nepal, one of the world’s poorest countries, is no exception to this trend, with lung cancer as the leading causes of cancer deaths. Despite this, limited data is available on the environmental and behavioral risk factors that contribute to the lung cancer etiology in Nepal. The objectives of this dissertation are to: 1) investigate the ethnic differences in consumption of local tobacco products and their role in lung cancer risk in Nepal; 2) evaluate urinary metabolite of 1,3-butadiene as a biomarker of exposure to combustion related household air pollution (CRHAP); 3) investigate the association between CRHAP exposure and lung cancer risk using urinary metabolite of 1,3-butadiene as a biomarker of exposure; 4) investigate the association between CRHAP exposure and lung cancer risk using questionnaire based measure of exposure. Lung cancer cases (n=606) and frequency matched controls (N=606) were recruited from B.P. Koirala Memorial Cancer Hospital. We obtained biological samples and information on lifestyles including cooking habits and type of fuels used. We used liquid chromatograph tandem mass spectrometer (LC-MS/MS) to quantify urinary metabolites of 1,3-butadiene in urine samples. We employed a combination of logistic and linear regression models to detect any exposure-disease associations while controlling for known confounding variables. Overall, we found that ethnic groups in Nepal use different tobacco products that have different differing cancer potency -we observed the highest odds ratios for the traditional tobacco products. The biomarker analysis showed strong evidence that monohydroxybutyl mercapturic acid is associated with biomass fuel use among participants. However, we did not find significant association between urinary MHMBA and lung cancer risk. When we used questionnaire based measure of exposure to household air pollution, we observed significant, dose-response associations between CRHAP exposure and lung cancer risk, particularly among never-smokers. Our results show that important role of local tobacco products in lung cancer risk in Nepal. Furthermore, we demonstrate that CRHAP exposure is a risk factor for lung cancer risk, independent of tobacco smoking.

A cost-efficiency and health benefit approach to improve urban air quality

When ambient air quality standards established in the EU Directive 2008/50/EC are exceeded, Member States are obliged to develop and implement Air Quality Plans (AQP) to improve air quality and health. Notwithstanding the achievements in emission reductions and air quality improvement, additional efforts need to be undertaken to improve air quality in a sustainable way - i.e. through a cost-efficiency approach. This work was developed in the scope of the recently concluded MAPLIA project "Moving from Air Pollution to Local Integrated Assessment", and focuses on the definition and assessment of emission abatement measures and their associated costs, air quality and health impacts and benefits by means of air quality modelling tools, health impact functions and cost-efficiency analysis. The MAPLIA system was applied to the Grande Porto urban area (Portugal), addressing PM10 and NOx as the most important pollutants in the region. Four different measures to reduce PM10 and NOx emissions were defined and characterized in terms of emissions and implementation costs, and combined into 15 emission scenarios, simulated by the TAPM air quality modelling tool. Air pollutant concentration fields were then used to estimate health benefits in terms of avoided costs (external costs), using dose-response health impact functions. Results revealed that, among the 15 scenarios analysed, the scenario including all 4 measures lead to a total net benefit of 0.3M€·y(-1). The largest net benefit is obtained for the scenario considering the conversion of 50% of open fire places into heat recovery wood stoves. Although the implementation costs of this measure are high, the benefits outweigh the costs. Research outcomes confirm that the MAPLIA system is useful for policy decision support on air quality improvement strategies, and could be applied to other urban areas where AQP need to be implemented and monitored.

Caracterização transcricional dos genes CTR1 e ATP7B no peixe Poecilia vivipara: efeitos do cobre e da salinidade

Em peixes, o cobre (Cu) é absorvido a partir da água, via branquial, e pela ingestão de água e alimento, via gastrintestinal. Para evitar reações não específicas prejudiciais e suprir proteínas dependentes de Cu, existem transportadores específicos, como as proteínas de absorção de alta afinidade ao Cu (CTR1) e as Cu-ATPases (ATP7), que auxiliam na translocação intracelular do metal. No presente estudo, os genes CTR1 e ATP7B foram identificados em Poecilia vivipara e os seus transcritos foram quantificados por RT-qPCR nas brânquias, no fígado e no intestino de guarús expostos (96 h) ao Cu (0, 5, 9 e 20 µg/L) em água doce e salgada (salinidade 24). Foram identificadas novas sequências nucleotídicas dos genes CTR1 (1560 pb, completa) e ATP7B (617 pb, parcial), as quais tiveram altos valores de identidade com as descritas para Fundulus heteroclitus (CTR1=81%) e Sparus aurata (ATP7B=81%). A análise por RT-qPCR indicou níveis de transcrição para CTR1 e ATP7B em todos os tecidos analisados. Em guarús na água doce, a maior expressão da CTR1 e da ATP7B se deu no fígado. Em guarús na água salgada, a maior expressão da CTR1 ocorreu no intestino, enquanto a da ATP7B se deu no fígado e intestino. Na água doce, a exposição ao Cu aumentou o conteúdo branquial e hepático de Cu, diminuiu os transcritos de CTR1 e ATP7B nas brânquias e aumentou os transcritos destes genes no fígado, sem alterar o conteúdo corporal de Cu. Na água salgada, a exposição ao Cu aumentou o conteúdo de Cu e diminuiu o transcrito de ATP7B no intestino, sem alterar o conteúdo corporal de Cu nos P. vivipara. Estes resultados indicam que a homeostasia do Cu em P. vivipara envolve a redução da expressão do CTR1 e ATP7B nas brânquias (água doce) e intestino (água salgada) para limitar a absorção do Cu e o aumento da expressão destes genes no fígado (água doce) para facilitar o armazenamento e desintoxicação do Cu.

Effects of Exposure to the Sound from Seismic Airguns on Pallid Sturgeon and Paddlefish - Data Set

Dataset for publication in PLOS One

Investigations of the Toxic Effect of Silver Nanoparticles on Mammalian Cell Lines

Silver nanoparticles are widely used for many applications. In this study silver nanoparticles have been tested for their toxic effect on fibroblasts (NIH-3T3), on a human lung adenocarcinoma epithelial cell line (A-549), on PC-12-cells, a rat adrenal pheochromocytoma cell line, and on HEP-G2-cells, a human hepatocellular carcinoma cell line. The viability of the cells cultivated with different concentrations of silver was determined by the MTT assay, a photometric method to determine cell metabolism. Dose-response curves were extrapolated and IC50, total lethal concentration (TLC), and no observable adverse effect concentration (NOAEC) values were calculated for each cell line. As another approach, ECIS (electric-cell-substrate-impedance-sensing) an automated method to monitor cellular behavior in real-time was applied to observe cells cultivated with silver nanoparticles. To identify the type of cell death the membrane integrity was analyzed by measurements of the lactate dehydrogenase releases and by determination of the caspase 3/7 activity. To ensure that the cytotoxic effect of silver nanoparticles is not traced back to the presence of Ag+ ions in the suspension, an Ag+ salt (AgNO3) has been examined at the same concentration of Ag+ present in the silver nanoparticle suspension that is assuming that the Ag particles are completely available as Ag+ ions.

Granulocyte-colony stimulating factor in experimental stroke and its effects on infarct size and functional outcome: a systematic review

Background Granulocyte-colony stimulating factor (G-CSF) shows promise as a treatment for stroke. This systematic review assesses G-CSF in experimental ischaemic stroke. Methods Relevant studies were identified with searches of Medline, Embase and PubMed. Data were extracted on stroke lesion size, neurological outcome and quality, and analysed using Cochrane Review Manager using random effects models; results are expressed as standardised mean difference (SMD) and odds ratio (OR). Results Data were included from 19 publications incorporating 666 animals. G-CSF reduced lesion size significantly in transient (SMD -1.63, p<0.00001) but not permanent (SMD -1.56, p=0.11) focal models of ischaemia. Lesion size was reduced at all doses and with treatment commenced within 4 hours of transient ischaemia. Neurological deficit (SMD -1.37, p=0.0004) and limb placement (SMD -1.88, p=0.003) improved with G-CSF; however, locomotor activity (>4 weeks post ischaemia) was not (SMD 0.76, p=0.35). Death (OR 0.27, p<0.0001) was reduced with G-CSF. Median study quality was 4 (range 0-7/8); Egger’s test suggested significant publication bias (p=0.001). Conclusions G-CSF significantly reduced lesion size in transient but not permanent models of ischaemic stroke. Motor impairment and death were also reduced. Further studies assessing dose-response, administration time, length of ischaemia and long-term functional recovery are needed.

An Analysis of Colombian Power Market Price Behavior from an Industrial Organization Perspective

We analyze the behavior of spot prices in the Colombian wholesale power market, using a series of models derived from industrial organization theory -- We first create a Cournot-based model that simulates the strategic behavior of the market-leader power generators, which we use to estimate two industrial organization variables, the Index of Residual Demand and the Herfindahl-Hirschman Index (HHI) -- We use these variables to create VAR models that estimate spot prices and power market impulse-response relationships -- The results from these models show that hydroelectric generators can use their water storage capability strategically to affect off-peak prices primarily, while the thermal generators can manage their capacity strategically to affect on-peak prices -- In addition, shocks to the Index of Residual Capacity and to the HHI cause spot price fluctuations, which can be interpreted as the generators´ strategic response to these shocks

Silenciamento do canal de potássio Eag1 potencializa efeitos da temozolomida em células U-87 MG de glioblastoma multiforme

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2015.