El análisis mediante RNA-seq y técnicas de captura de imagen de la interacción melón-Podosphaera xanthii revela modulación de la fotosíntesis y del metabolismo secundario de la planta por el patógeno

La familia de las cucurbitáceas incluye especies con gran relevancia económica entre las que destacan melón, sandía, calabacín, pepino y calabaza. Estos cultivos se ven afectados, entre otros, por el hongo biotrofo obligado Podosphaera xanthii, principal agente causal del oídio de las cucurbitáceas. El conocimiento sobre las bases moleculares de las interacciones entre P. xanthii y las diferentes especies de cucurbitáceas es, aún, muy limitado. Por ello, en este trabajo se ha realizado un análisis RNA-seq con el fin de conocer los cambios de expresión génica ocurridos en melón durante los primeros estadios de la enfermedad (24, 48 y 72 hpi). Además, estas fases tempranas de la enfermedad también fueron estudiadas usando técnicas de captura de imágenes como fluorescencia multiespectral y termografía. El análisis bioinformático permitió detectar 1.114 genes de la planta diferencialmente expresados a 24 h, 3.785 a 48 h y 4.226 a 72 h. El posterior enriquecimiento funcional reveló que los principales procesos que se estaban viendo modulados durante la infección eran la fotosíntesis y varias rutas metabólicas relacionadas con la defensa vegetal, resultados que fueron corroborados mediante las técnicas de captura de imagen. La combinación de ambas técnicas nos ha permitido comprender mejor el desarrollo de esta enfermedad desde dos enfoques diferentes pero complementarios e integradores.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Este trabajo ha sido financiado por el Ministerio de Economía y Competitividad (AGL2013-41939-R; AGL2016-76216-C2-1-R) cofinanciado con fondos FEDER (UE). Álvaro Polonio es beneficiario de un contrato predoctoral para la formación de doctores del Ministerio de Economía y Competitividad. Los autores también agradecen ayudas de la Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech, para la asistencia a este congreso

Evolution of the threshold temperature definition of a heat wave vs. evolution of the minimum mortality temperature: a case study in Spain during the 1983–2018 period

An area of current study concerns analysis of the possible adaptation of the population to heat, based on the temporal evolution of the minimum mortality temperature (MMT). It is important to know how is the evolution of the threshold temperatures (Tthreshold) due to these temperatures provide the basis for the activation of public health prevention plans against high temperatures. The objective of this study was to analyze the temporal evolution of threshold temperatures (Tthreshold) produced in different Spanish regions during the 1983–2018 period and to compare this evolution with the evolution of MMT. The dependent variable used was the raw rate of daily mortality due to natural causes ICD X: (A00-R99) for the considered period. The independent variable was maximum daily temperature (Tmax) during the summer months registered in the reference observatory of each region. Threshold values were determined using dispersion diagrams (annual) of the prewhitened series of mortality temperatures and Tmax. Later, linear fit models were carried out between the different values of Tthreshold throughout the study period, which permitted detecting the annual rate of change in Tthreshold.This research project was funded by the Carlos III Health Institute (ISCIII) under file number ENPY 470/19 and is supported by the Biodiversity Foundation of the Ministry for Ecological Transition and Demographic Challenge, in addition to the research projects ISCIII: ENPY107/18 and ENPY 376/1

Implications of global pricing policies on access to innovative drugs: : the case of trastuzumab in seven Latin American countries

Background: Differential pricing, based on countries’ purchasing power, is recommended by the WHO to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage and accessibility for patients with breast cancer in Latin America (LA). Methods: A Markov model was designed to estimate life years (LYs), quality-adjusted life years (QALYs) and costs from a health care perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country. Findings: Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 US dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0% probability that trastuzumab is CE if the willingness-to-pay (WTP) threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3% and 26.6% respectively). Trastuzumab price would need to decrease between 69.6% to 94.9% to became CE in LA. Interpretation: Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries

Modelling the spatial risk of malaria through probability distribution of Anopheles maculipennis s.l. and imported cases

Malaria remains one of the most important infectious diseases globally due to its high incidence and mortality rates. The influx of infected cases from endemic to non-endemic malaria regions like Europe has resulted in a public health concern over sporadic local outbreaks. This is facilitated by the continued presence of competent Anopheles vectors in non-endemic countries. We modelled the potential distribution of the main malaria vector across Spain using the ensemble of eight modelling techniques based on environmental parameters and the Anopheles maculipennis s.l. presence/absence data collected from 2000 to 2020. We then combined this map with the number of imported malaria cases in each municipality to detect the geographic hot spots with a higher risk of local malaria transmission. The malaria vector occurred preferentially in irrigated lands characterized by warm climate conditions and moderate annual precipitation. Some areas surrounding irrigated lands in northern Spain (e.g. Zaragoza, Logroño), mainland areas (e.g. Madrid, Toledo) and in the South (e.g. Huelva), presented a significant likelihood of A. maculipennis s.l. occurrence, with a large overlap with the presence of imported cases of malaria. While the risk of malaria re-emergence in Spain is low, it is not evenly distributed throughout the country. The four recorded local cases of mosquito-borne transmission occurred in areas with a high overlap of imported cases and mosquito presence. Integrating mosquito distribution with human incidence cases provides an effective tool for the quantification of large-scale geographic variation in transmission risk and pinpointing priority areas for targeted surveillance and prevention

CD133-directed CAR T-cells for MLL leukemia: on-target, off-tumor myeloablative toxicity

This work has been supported by the European Research Council (CoG-2014-646903, PoC-2018-811220) to PM, the Spanish Ministry of Economy and Competitiveness (MINECO, SAF-SAF2016-80481- R, BIO2017-85364-R) to PM and EE, the Generalitat de Catalunya (SGR330, SGR102 and PERIS) to PM and EE, the Spanish Association against cancer (AECC-CI-2015) to CB, and the Health Institute Carlos III (ISCIII/FEDER, PI14-01191) to CB. PM also acknowledges financial support from the Obra Social La Caixa-Fundaciò Josep Carreras. SRZ and TV are supported by a Marie Curie fellowships. OM is supported by the Catalan Government through a Beatriu de Pinos fellowship. MB is supported by MINECO through a PhD scholarship. PM is an investigator of the Spanish Cell Therapy cooperative network (TERCEL)

Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution. METHODS: We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population. RESULTS: The proportion of lung cancers in never- and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5-7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions. DISCUSSION: We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10-20 ug/m3, whereas levels in Italy are around 30 or 40, or higher).Therefore, further reduction in exposure levels below 30 ug/m3 would correspond to additional lung cancer cases prevented, and our estimate of 5-7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe.Published versio

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors

Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient ' s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients

Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study

In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse. statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P=0.02), vitamin E (P =0.04) and alcohol (P=0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P=0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but Such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances