Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts

This study investigates relationships between EMT and bone invasion by OSCC. Three OSCC cell lines, SCC25, HN5, and Tca8113 were artificially induced to display EMT by adding 5 ng/mL of TGF-β1 to culture media for 1–3 days. Cell morphology and phenotypic changes was examined by immunocytochemical staining of CK and VIM. EMT markers, cell-invasion factors, and osteoclast-related molecules were analysed at mRNA, gelatine and protein levels by real-time PCR, gelatine zymography and Western blotting respectively. Mature osteoclasts differentiated from Raw264.7 cells were treated by conditioned medium (CM) of OSCC cells with/without TGF-β1. Immunohistochemistry was performed to validate proteins of CK, VIM, E-cad and Snail1 in OSCC tissue samples with bone invasion. Results showed minimal staining of VIM was found in SCC25 and HN5, while Tca8113 cells stained strongly. EMT markers Twist1 and N-cad were up-regulated; Snail1 and E-cad down-regulated in all cells. Of factors associated with invasion, MMP-2 was unchanged and MMP-9 increased in SCC25 and Tca8113, while MMP-2 was increased and MMP-9 unchanged in HN5. For osteoclast-related molecules, both MT1-MMP and RANKL were up-regulated, while OPG was down-regulated in all cells. CM of OSCC cells pre-treated with TGF-β1 showed to prolong survival of osteoclasts up to 4 days. All target molecules were validated in OSCC samples of bone invasion. These findings suggest that TGF-β1 not only induces EMT to increase the capacity of OSCC for invasion, but also promotes factors which prolong osteoclast survival. TGF-β1 may enhance the ability of MMP2/9 in resorbing bone and favouring invasion of cancer cells

A comparison of health state utility values associated with oral potentially malignant disorders and oral cancer in Sri Lanka assessed using the EQ-5D-3 L and the EORTC-8D

Background: It has been suggested that the EQ-5D-3 L preference-based measure of health outcome lacks sensitivity to discriminate between health states in cancer patients. An alternative approach is to use a disease (cancer) specific preference-based measure, such as the EORTC-8D. A limited number of comparisons have been made between generic and disease specific preference-based measures. The aim of this study was to compare the utility scores from the EQ-5D-3 L and the EORTC-8D in a group of patients with oral cancer or with oral potentially malignant disorders (OPMD). Methods: Patients (n = 151) with OPMD or oral cancer were recruited consecutively from six hospitals in Sri Lanka. All participants completed both the EQ-5D-3 L and the EORTC's QLQC-30 instrument. The Sri Lankan EQ-5D-3 L and EORTC-8D scoring algorithms were employed to estimate utility scores. The utility scores from the two instruments were compared for discrimination, responsiveness and correlation. Results: There were significant differences across the two utility scores. The EQ-5D-3 L showed better discrimination than EORTC-8D with higher effect sizes. There were higher ceiling effects observed in the EQ-5D-3 L. There was poor correlation between the dimensions of the two instruments except for the mobility and physical functions. Conclusion: The two instruments captured different aspects of quality of life. The EQ-5D-3 L demonstrated better discrimination than the EORTC-8D. In mild conditions EORTC-8D was more responsive and we recommend further validation of this instrument in diverse cancer conditions

A comparison of health state utility values associated with oral potentially malignant disorders and oral cancer in Sri Lanka assessed using the EQ-5D-3 L and the EORTC-8D

Background: It has been suggested that the EQ-5D-3 L preference-based measure of health outcome lacks sensitivity to discriminate between health states in cancer patients. An alternative approach is to use a disease (cancer) specific preference-based measure, such as the EORTC-8D. A limited number of comparisons have been made between generic and disease specific preference-based measures. The aim of this study was to compare the utility scores from the EQ-5D-3 L and the EORTC-8D in a group of patients with oral cancer or with oral potentially malignant disorders (OPMD). Methods: Patients (n = 151) with OPMD or oral cancer were recruited consecutively from six hospitals in Sri Lanka. All participants completed both the EQ-5D-3 L and the EORTC's QLQC-30 instrument. The Sri Lankan EQ-5D-3 L and EORTC-8D scoring algorithms were employed to estimate utility scores. The utility scores from the two instruments were compared for discrimination, responsiveness and correlation. Results: There were significant differences across the two utility scores. The EQ-5D-3 L showed better discrimination than EORTC-8D with higher effect sizes. There were higher ceiling effects observed in the EQ-5D-3 L. There was poor correlation between the dimensions of the two instruments except for the mobility and physical functions. Conclusion: The two instruments captured different aspects of quality of life. The EQ-5D-3 L demonstrated better discrimination than the EORTC-8D. In mild conditions EORTC-8D was more responsive and we recommend further validation of this instrument in diverse cancer conditions

Fatores de risco ambientais associados à cárie dentária nas crianças: uma revisão de quatro estudos na Indonésia

There is growing concern over studying the environmental impacts on human health. Among the world’s population, children are particularly vulnerable to environmental threats.Currently, in certain areas of Indonesia, there are significant problems with water quality, especially as many consume surface water for drinking. There is evidence that this contributes to tooth decay – the process of dental caries. Furthermore, teeth provide an excellent chronological record of nutritional status and trace metal exposure during human development.This paper provides an overview of risk factors for dental caries and reviews four epidemiological and laboratory studies that have addressed these issues in Indonesia. First, Winanto in 1993 showed that acidity and high tin (Sn) concentrations in drinking water are associated with the erosion of permanent teeth in children living close to a tin mining area. Second, Wulandari in 2009, using Graphite Furnace Atomic Absorption Spectrometry (GFAAS), showed that deciduous teeth containing high concentration of lead (Pb) have 3 times higher risks of contracting caries. Third, Satrio in 2010 compared the dental status of children who consumed rain water with those using other sources of drinking water: this revealed that low concentration of Fluoride in drinking water contributes 19 times higher risk of dental caries and low pH 22 times the risk compared to water of neutral pH. Fourth, Musadad in 2009 undertook an ecological study on the effect of drinking water quality in relation to dental caries and revealed significant associations with acidity, total water consumption, household expenditure and the distance from a subject’s residence to the nearest dental health provider.Thus, in Indonesia, tooth decay is not only associated with poor diet and poor oral hygiene; it also reflects poor environment.Existe una creciente preocupación por el estudio de los impactos ambientales en la salud humana. Los niños son particularmente vulnerables a las amenazas ambientales en cualquier parte del mundo.Actualmente, en ciertas zonas de Indonesia, existen problemas con la calidad del agua, especialmente con el uso de aguas superficiales como fuente de agua potable para consumo humano.Hay evidencias de que ello contribuye a los procesos de aparición de caries dental. Por otra parte, los dientes proporcionan un excelente registro cronológico del estado nutricional y de la exposición a metales durante las etapas de desarrollo humano.Este documento ofrece una visión general de los factores de riesgo de la caries y revisa cuatro estudios epidemiológicos y de laboratorio que han abordado estas cuestiones en Indonesia. En primer lugar, Winanto en 1993 mostró que la acidez y las altas concentraciones de estaño (Sn) en el agua potable están asociadas con la erosión de los dientes permanentes de los niños que viven cerca de una zona minera de estaño. En segundo lugar, Wulandari en 2009, utilizando espectrometría de absorción atómica en horno de grafito, mostró que los dientes temporales que contienen altas concentraciones de plomo (Pb) tienen un riesgo tres veces mayor de contraer caries. En tercer lugar, Satrio en 2010 comparó el estado dental de los niños que consumen agua procedente de la lluvia con los que utilizan otras fuentes de agua potable: esto reveló que el riesgo de aparición de caries dentales aumenta 19 veces con una baja concentración de flúor en el agua de bebida y 22 veces con un pH bajo en comparación con agua de pH neutro. En cuarto lugar, Musadad en 2009 llevó a cabo un estudio ecológico sobre el efecto de la calidad del agua potable en relación con la caries dental y reveló asociaciones significativas con la acidez, con la cantidad de consumo de agua, con el gasto de los hogares y con la distancia entre el domicilio y el proveedor de salud dental más cercano.Por tanto, en Indonesia, la caries no solo se asocia con una mala alimentación y una higiene bucal deficiente, sino que también refleja las condiciones ambientales.Há uma crescente preocupação com o estudo dos impactos do ambiente na saúde humana. Entre a população do mundo, as crianças são particularmente vulneráveis às ameaças ambientais.Atualmente, em algumas áreas da Indonésia, existem problemas significativos com a qualidade da água, especialmente devido ao uso de muitas águas superficiais para consumo humano. Há evidência de que isto contribui para o processo de cárie dentária. Além disso, os dentes fornecem um excelente registo cronológico do estado nutricional e indicação da exposição a metais durante o desenvolvimento humano.Este artigo fornece uma visão geral dos fatores de risco para a cárie dentária e as revisões de quatro estudos epidemiológicos e laboratoriais que abordaram este assunto na Indonésia. Primeiro estudo: Winanto em 1993 mostrou que a acidez e concentrações elevadas de estanho (Sn) na água para consumo humano estão associadas com a erosão dos dentes permanentes em crianças que vivem perto de uma exploração mineira de estanho. Segundo estudo: Wulandari em 2009, recorrendo à espectrometria de absorção atômica com forno de grafite (GFAAS), mostrou que dentes decíduos que contenham uma alta concentração de chumbo (Pb) têm três vezes maior risco de contrair cárie. Terceiro estudo: Satrio em 2010, comparou o estado dos dentes entre as crianças que consumiam água da chuva e as crianças que consumiam água de outras origens. Este revelou que a baixa concentração de fluor na água contribui para aumentar 19 vezes o risco de cáries e que o consumo de água com pH baixo aumenta 22 vezes o risco de cárie quando comparado com o consumo de água com pH neutro. Quarto estudo: Musadad em 2009, realizou um estudo ecológico sobre o efeito da qualidade da água potável em relação à cárie dentária e revelou associação significativa com a acidez, a quantidade de água consumida, a despesa das famílias e a distância da residência a um serviço de medicina dentária. Assim, na Indonésia, a cárie dentária não está associada apenas com a má alimentação e má higiene oral, mas também reflete a existência de más condições ambientais

The evolution of representation in simple cognitive networks

Representations are internal models of the environment that can provide guidance to a behaving agent, even in the absence of sensory information. It is not clear how representations are developed and whether or not they are necessary or even essential for intelligent behavior. We argue here that the ability to represent relevant features of the environment is the expected consequence of an adaptive process, give a formal definition of representation based on information theory, and quantify it with a measure R. To measure how R changes over time, we evolve two types of networks---an artificial neural network and a network of hidden Markov gates---to solve a categorization task using a genetic algorithm. We find that the capacity to represent increases during evolutionary adaptation, and that agents form representations of their environment during their lifetime. This ability allows the agents to act on sensorial inputs in the context of their acquired representations and enables complex and context-dependent behavior. We examine which concepts (features of the environment) our networks are representing, how the representations are logically encoded in the networks, and how they form as an agent behaves to solve a task. We conclude that R should be able to quantify the representations within any cognitive system, and should be predictive of an agent's long-term adaptive success.Comment: 36 pages, 10 figures, one Tabl

EQ-5D-3L Derived Population Norms for Health Related Quality of Life in Sri Lanka

Background Health Related Quality of Life (HRQoL) is an important outcome measure in health economic evaluation that guides health resource allocations. Population norms for HRQoL are an essential ingredient in health economics and in the evaluation of population health. The aim of this study was to produce EQ-5D-3L-derived population norms for Sri Lanka. Method A population sample (n =  780) was selected from four districts of Sri Lanka. A stratified cluster sampling approach with probability proportionate to size was employed. Twenty six clusters of 30 participants each were selected; each participant completed the EQ-5D-3L in a face-to-face interview. Utility weights for their EQ-5D-3L health states were assigned using the Sri Lankan EQ-5D-3L algorithm. The population norms are reported by age and socio-economic variables. Results The EQ-5D-3L was completed by 736 people, representing a 94% response rate. Sixty per cent of the sample reported being in full health. The percentage of people responding to any problems in the five EQ-5D-3L dimensions increased with age. The mean EQ-5D-3L weight was 0.85 (SD 0.008; 95%CI 0.84-0.87). The mean EQ-5D-3L weight was significantly associated with age, housing type, disease experience and religiosity. People above 70 years of age were 7.5 times more likely to report mobility problems and 3.7 times more likely to report pain/discomfort than those aged 18-29 years. Those with a tertiary education were five times less likely to report any HRQoL problems than those without a tertiary education. A person living in a shanty was 4.3 more likely to have problems in usual activities than a person living in a single house. Conclusion The population norms in Sri Lanka vary with socio-demographic characteristics. The socioeconomically disadvantaged have a lower HRQoL. The trends of population norms observed in this lower middle income country were generally similar to those previously reported in high income countries

Breath biopsy, a novel technology to identify head and neck squamous cell carcinoma: A systematic review

Head and neck cancers are a heterogeneous group of neoplasms, which together comprise the sixth most common cancer globally. Breath biopsies are a non-invasive clinical investigation that detect volatile organic compounds (VOCs) in exhaled breath. This systematic review examines current applications of breath biopsy for the diagnosis of head and neck squamous cell carcinoma (HNSCC), including data on efficacy and utility, and speculates on the future uses of this non-invasive detection method. Medline, PubMed, Web of Science, Cochrane and Scopus, as well as the grey literature were searched using a search strategy developed to identify relevant studies on the role of breath biopsy in the diagnosis of HNSCC. All included studies were subject to a thorough methodological quality assessment. The initial search generated a total of 1443 articles, 20 of which were eligible for review. A total of 660 HNSCC samples were investigated across the included studies. 3,7-dimethylundecane and benzaldehyde were among several VOCs to be significantly correlated with the presence of HNSCC compared to healthy controls. We show that current breath biopsy methods have high accuracy, specificity and sensitivity for identifying HNSCC. However, further studies are needed given the reported poor quality of the included studies

Long-term trends in anthropogenic land use in Siberia and the Russian Far East : a case study synthesis from Landsat

As globally important forested areas situated in a context of dramatic socio-economic changes, Siberia and the Russian Far East (RFE) are important regions to monitor for anthropogenic land-use trends. Therefore, we compiled decadal Landsat-derived land-cover and land-use data for eight dominantly rural case study sites in these regions and focused on trends associated with settlements, agriculture, logging, and roads 1975-2010. Several key spatial-temporal trends emerged from the integrated landscape-scale analyses. First, road building increased in all case study sites over the 35-year period, despite widespread socio-economic decline post-1990. Second, increase in settlements area was negligible over all sites. Third, increased road building, largely of minor roads, was especially high in more rugged and remote RFE case study sites not associated with greater agriculture extent or settlement densities. High demands for wood export coupled with the expansion of commercial timber harvest leases starting in the mid-1990s are likely among leading reasons for an increase in roads. Fourth, although fire was the dominant disturbance over all sites and dates combined, logging exerted a strong land-use pattern, serving as a reminder that considering local anthropogenic landscapes is important, especially in Siberia and the RFE, which represent almost 10% of the Earth's terrestrial land surface. The paper concludes by identifying remaining research needs regarding anthropogenic land use in the region: more frequent moderate spatial resolution imagery and greater access to more finely resolved statistical and other spatial data will enable further research. Social media abstract Landsat reveals long-term anthropogenic land-use trends in Siberia and Russian Far EastPeer reviewe

Symbolic Software for the Painleve Test of Nonlinear Ordinary and Partial Differential Equations

The automation of the traditional Painleve test in Mathematica is discussed. The package PainleveTest.m allows for the testing of polynomial systems of ordinary and partial differential equations which may be parameterized by arbitrary functions (or constants). Except where limited by memory, there is no restriction on the number of independent or dependent variables. The package is quite robust in determining all the possible dominant behaviors of the Laurent series solutions of the differential equation. The omission of valid dominant behaviors is a common problem in many implementations of the Painleve test, and these omissions often lead to erroneous results. Finally, our package is compared with the other available implementations of the Painleve test.Comment: Published in the Journal of Nonlinear Mathematical Physics (http://www.sm.luth.se/math/JNMP/), vol. 13(1), pp. 90-110 (Feb. 2006). The software can be downloaded at either http://www.douglasbaldwin.com or http://www.mines.edu/fs_home/wherema