Cancer drug resistance induced by EMT: novel therapeutic strategies

Over the last decade, important clinical benefits have been achieved in cancer patients by using drug-targeting strategies. Nevertheless, drug resistance is still a major problem in most cancer therapies. Epithelial-mesenchymal plasticity (EMP) and tumour microenvironment have been described as limiting factors for effective treatment in many cancer types. Moreover, epithelial-to-mesenchymal transition (EMT) has also been associated with therapy resistance in many different preclinical models, although limited evidence has been obtained from clinical studies and clinical samples. In this review, we particularly deepen into the mechanisms of which intermediate epithelial/mesenchymal (E/M) states and its interconnection to microenvironment influence therapy resistance. We also describe how the use of bioinformatics and pharmacogenomics will help to figure out the biological impact of the EMT on drug resistance and to develop novel pharmacological approaches in the future

Age at menopause in Latin America

OBJECTIVE: To assess the age at menopause (AM) in Latin America urban areas. DESIGN: A total of 17,150 healthy women, aged 40 to 59 years, accompanying patients to healthcare centers in 47 cities of 15 Latin American countries, were surveyed regarding their age, educational level, healthcare coverage, history of gynecological surgery, smoking habit, presence of menses, and the use of contraception or hormone therapy at menopause. The AM was calculated using logit analysis. RESULTS: The mean age of the entire sample was 49.4 ± 5.5 years. Mean educational level was 9.9 ± 4.5 years, and the use of hormone therapy and oral contraception was 22.1% and 7.9%, respectively. The median AM of women in all centers was 48.6 years, ranging from 43.8 years in Asuncion (Paraguay) to 53 years in Cartagena de Indias (Colombia). Logistic regression analysis determined that women aged 49 living in cities at 2,000 meters or more above sea level (OR = 2.0, 95% CI: 1.4-2.9, P less than 0.001) and those with lower educational level (OR = 1.9, 95% CI: 1.3-2.8, P less than 0.001) or living in countries with low gross national product (OR = 2.1, 95% CI: 1.5-2.9, P less than 0.001) were more prone to an earlier onset of menopause. CONCLUSIONS: The AM varies widely in Latin America. Lower income and related poverty conditions influence the onset of menopause. © 2006 by The North American Menopause Society

Impact of Human Management on the Genetic Variation of Wild Pepper, Capsicum annuum var. glabriusculum

Management of wild peppers in Mexico has occurred for a long time without clear phenotypic signs of domestication. However, pre-domestication management could have implications for the population's genetic richness. To test this hypothesis we analysed 27 wild (W), let standing (LS) and cultivated (C) populations, plus 7 samples from local markets (LM), with nine polymorphic microsatellite markers. Two hundred and fifty two alleles were identified, averaging 28 per locus. Allele number was higher in W, and 15 and 40% less in LS and C populations, respectively. Genetic variation had a significant population structure. In W populations, structure was associated with ecological and geographic areas according to isolation by distance. When LM and C populations where included in the analysis, differentiation was no longer apparent. Most LM were related to distant populations from Sierra Madre Oriental, which represents their probable origin. Historical demography shows a recent decline in all W populations. Thus, pre-domestication human management is associated with a significant reduction of genetic diversity and with a loss of differentiation suggesting movement among regions by man. Measures to conserve wild and managed populations should be implemented to maintain the source and the architecture of genetic variation in this important crop relative

Predicting River Macroinvertebrate Communities Distributional Shifts under Future Global Change Scenarios in the Spanish Mediterranean Area

Several studies on global change over the next century predict increases in mean air temperatures of between 1°C to 5°C that would affect not only water temperature but also river flow. Climate is the predominant environmental driver of thermal and flow regimes of freshwater ecosystems, determining survival, growth, metabolism, phenology and behaviour as well as biotic interactions of aquatic fauna. Thus, these changes would also have consequences for species phenology, their distribution range, and the composition and dynamics of communities. These effects are expected to be especially severe in the Mediterranean basin due its particular climate conditions, seriously threatening Southern European ecosystems. In addition, species with restricted distributions and narrow ecological requirements, such as those living in the headwaters of rivers, will be severely affected. The study area corresponds to the Spanish Mediterranean and Balearic Islands, delimited by the Köppen climate boundary. With the application of the MEDPACS (MEDiterranean Prediction And Classification System) predictive approach, the macroinvertebrate community was predicted for current conditions and compared with three posible scenarios of watertemperature increase and its associated water flow reductions. The results indicate that the aquatic macroinvertebrate communities will undergo a drastic impact, with reductions in taxa richness for each scenario in relation to simulated current conditions, accompanied by changes in the taxa distribution pattern. Accordingly, the distribution area of most of the taxa (65.96%) inhabiting the mid-high elevations would contract and rise in altitude. Thus, families containing a great number of generalist species will move upstream to colonize new zones with lower water temperatures. By contrast, more vulnerable taxa will undergo reductions in their distribution area.This work was funded by GUADALMED-II (REN2001-3438-C07-06/HID), a project of excellence from “Junta de Andalucía” (RNM-02654/FEDER), the Spanish “Ministerio de Ciencia e Innovación” (CGL2007-61856/BOS), projects and a collaboration agreement between the “Spanish Ministerio de Medio Ambiente, Medio Rural y Marino” and the University of Granada (21.812-0062/8511)

Validation and psychometric analysis of the Internet Addiction Test in Spanish among college students

BACKGROUND: The wide use of the Internet in the workplace, academic or social field, can have an impact on daily life. One of the most used questionnaires worldwide to analyse these problems is the Internet Addiction Test (IAT). Our aim was to validate a Spanish version of the IAT and analyse its psychometric properties. METHODS: Population of study were college students participating in the uniHcos project (Universities of Granada, Huelva, Jaén, León, Salamanca, and Vigo). The questionnaire was translated and back-translated by two native English speakers. Reliability of scores was analysed using Pearson's correlation coefficient and agreement was analysed using the Bland-Altman and Kappa techniques. Test dimensions were analysed by exploratory and confirmatory factor analysis. RESULTS: The reliability of scores was good (r = 0.899, Kappa = 0.650 and mean difference using Bland-Altman = -3.5). The psychometric assessment identified two factors (Emotional Investment; Performance and Time Management) which explained 55 % of the variance (total internal consistency of 0.91) and only 19 items. The confirmatory analysis showed an acceptable goodness of fit, especially when items 6 and 8 were related (RMSEA = 0.07 90%IC = 0.06 - 0.08; WRMR = 1.01, CFI = 0.96; TLI = 0.95). The two dimensions were negatively correlated with age and positively correlated with time spent online, especially for the purposes of leisure and entertainment. DISCUSSION: The results show good reliability and psychometric properties of the Spanish version of IAT with a two-dimensional solution. This result is partially in concordance with previous validations of the IAT in other languages that have found uni- and multi-dimensional solutions using different methodologies. Moreover, we want to highlight the possibility that some item of this questionnaire is outdated due to the technological and lifestyles changes and should be not taken into account. CONCLUSION: The reliability and psychometric properties obtained in this study support the conclusion that this Spanish short version of the IAT represents a useful tool for the analysis of problems arising from misuse of the Internet

Strategic crossing of biomass and harvest index—source and sink—achieves genetic gains in wheat

To accelerate genetic gains in breeding, physiological trait (PT) characterization of candidate parents can help make more strategic crosses, increasing the probability of accumulating favorable alleles compared to crossing relatively uncharacterized lines. In this study, crosses were designed to complement “source” with “sink” traits, where at least one parent was selected for favorable expression of biomass and/or radiation use efficiency—source—and the other for sink-related traits like harvest-index, kernel weight and grains per spike. Female parents were selected from among genetic resources—including landraces and products of wide-crossing (i.e. synthetic wheat)—that had been evaluated in Mexico at high yield potential or under heat stress, while elite lines were used as males. Progeny of crosses were advanced to the F4 generation within Mexico, and F4-derived F5 and F6 generations were yield tested to populate four international nurseries, targeted to high yield environments (2nd and 3rd WYCYT) for yield potential, and heat stressed environments (2nd and 4th SATYN) for climate resilience, respectively. Each nursery was grown as multi-location yield trials. Genetic gains were achieved in both temperate and hot environments, with most new PT-derived lines expressing superior yield and biomass compared to local checks at almost all international sites. Furthermore, the tendency across all four nurseries indicated either the superiority of the best new PT lines compared with the CIMMYT elite checks, or the superiority of all new PT lines as a group compared with all checks, and in some cases, both. Results support—in a realistic breeding context—the hypothesis that yield and radiation use efficiency can be increased by improving source:sink balance, and validate the feasibility of incorporating exotic germplasm into mainstream breeding efforts to accelerate genetic gains for yield potential and climate resilience

Synthesis and evaluation of thiosemicarbazones functionalized with furyl moieties as new chemosensors for anion recognition

A family of heterocyclic thiosemicarbazone dyes (3a-f and 4) containing furyl groups were synthesized in good yields, characterized and their response in acetonitrile in the presence of selected anions was studied. Acetonitrile solutions of 3a-f and 4 show absorption bands in the 335-396 nm range which are modulated by the electron donor or acceptor strength of the heterocyclic systems appended to the thiosemicarbazone moiety. Fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulphate, nitrate, acetate and cyanide anions, were used in recognition studies. From these anions, only sensing features were seen for fluoride, cyanide, acetate and dihydrogen phosphate. Two clearly different chromo-fluorogenic behaviours were observed, (i) a small shift of the absorption band due to the coordination of the anions with the thiourea protons and (ii) the appearance of a new red shifted band due to deprotonation. For the latter effect, a change in the colour solution from pale yellow to purple was observed. Fluorescence studies were also in agreement with the different effects observed in the UV/Vis titrations. In this case, hydrogen bonding interactions were visible through the enhancement of the emission band, whereas deprotonation induced the appearance of a new red-shifted emission. Logarithms of stability constants for the two processes (complex formation + deprotonation) for receptors 3a-f in the presence of fluoride and acetate anions were determined from spectrophotometric titrations using the HypSpec V1.1.18 program. Semi-empirical calculations to evaluate the hydrogen-donating ability of the receptors and a prospective electrochemical characterization of compound 3b in the presence of fluoride were also performed.Fundação para a Ciência e a Tecnologia (FCT), Acções Integradas Luso-espanholas/CRUP, Generalitat Valenciana

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts