Rapid evolution and biogeographic spread in a colorectal cancer

How and when tumoral clones start spreading to surrounding and distant tissues is currently unclear. Here we leveraged a model-based evolutionary framework to investigate the demographic and biogeographic history of a colorectal cancer. Our analyses strongly support an early monoclonal metastatic colonization, followed by a rapid population expansion at both primary and secondary sites. Moreover, we infer a hematogenous metastatic spread under positive selection, plus the return of some tumoral cells from the liver back to the colon lymph nodes. This study illustrates how sophisticated techniques typical of organismal evolution can provide a detailed, quantitative picture of the complex tumoral dynamics over time and space.This work was supported by the European Research Council (ERC-617457- PHYLOCANCER awarded to D.P.) and by the Spanish Ministry of Economy and Competitiveness—MINECO (BFU2015-63774-P awarded to D.P.). D.P. receives further support from Xunta de Galicia. J.M.A. is currently supported by an AXA Research Fund Postdoctoral Fellowship. J.M.C.-T. is supported by Grant PI15/01501-FEDER from the Instituto de Salud Carlos III, Ministry of Science, Innovation and Universities, SpainS

Oral Function and Eating Habit Problems in People with Down Syndrome

Background: Down syndrome (DS) is a genetic disorder in which there is an increased risk of developing clinical comorbidities that require regular attention: health problems, alterations in maxillomandibular development, chewing and swallowing problems, as well as dietary habits that may influence diet and nutritional status. This study will analyze the frequency of occurrence of these factors with increasing age in this population. Methods: A descriptive cross-sectional study was conducted with 18 participants aged 30–45 years. The condition of orofacial structures, chewing and swallowing function and oral and eating habits were assessed to observe the frequency of occurrence of these problems with increasing age. Results: A high frequency of digestive problems was observed. There was also a presence of problems in the introduction of new tastes and consistencies. In addition, unilateral chewing was reported in 100% of the participants, severe anatomical dysfunction of the mandible/maxilla and high hypotonicity reflected in tongue movements. Conclusions: it is necessary to educate, through specific intervention protocols, the younger generations with DS, as well as their environment, as harmful habits are developed in childhood and consolidated throughout life

Rapid evolution and biogeographic spread in a colorectal cancer

How and when tumoral clones start spreading to surrounding and distant tissues is currently unclear. Here we leveraged a model-based evolutionary framework to investigate the demographic and biogeographic history of a colorectal cancer. Our analyses strongly support an early monoclonal metastatic colonization, followed by a rapid population expansion at both primary and secondary sites. Moreover, we infer a hematogenous metastatic spread under positive selection, plus the return of some tumoral cells from the liver back to the colon lymph nodes. This study illustrates how sophisticated techniques typical of organismal evolution can provide a detailed, quantitative picture of the complex tumoral dynamics over time and spaceEuropean Research Council | Ref. ERC-617457- PHYLOCANCERMinisterio de Economía y Competitividad | Ref. BFU2015-63774-PInstituto de Salud Carlos III | Ref. PI15/01501-FEDE

Removal of azo dyes orange II and reactive black 5 from aqueous solutions by adsorption on chitosan beads modified with choline chloride: urea deep eutectic solvent and FeO

The removal of the azo dyes Orange II (OII) and Reactive Black 5 (RB5) from aqueous solutions was studied using three types of adsorbents derived from chitosan: unmodified chitosan beads (un-Ch), chitosan beads tuned with a deep eutectic solvent (DES) composed of choline chloride:urea at a 1:2 molar ratio (Ch-DES), along with FeO nanoparticles added to chitosan and modified with DES (Ch-FeO-DES). Both dyes were effectively removed in 3–4 h when Ch-DES beads were used, at a dye concentration range of 25–50 mg/L. The modification with DES improved the removal efficiency to achieve increases of around 32% for OII and 17% for RB5. The adsorbent dosage and the initial dye concentration influenced the adsorption process. Isotherm adsorption models (Langmuir, Freundlich, and Temkin) and kinetic models (pseudo-first-order, pseudo-second-order, intraparticle diffusion, and Elovich models) were applied to identify the adsorption behavior. The process could be characterized by employing the pseudo-second-order kinetic model and fitting it to the monolayer Langmuir isotherm. The adsorption occurred on a monolayer with no interaction among dye molecules when electrostatic forces would determine the attaching of dye molecules on the adsorbent. OII was efficiently desorbed by an alkaline solution, while RB5 was more strongly attached. The adsorbent could be recycled, after regeneration with an acid solution, for at least 5 reuse cycles while still achieving effective OII removal. Reactivation with a diluted EDTA solution allowed the authors to recycle RB5-attached beads, achieving optimum removal in two further uses.Xunta de Galicia | Ref. GPC-ED431B 2020/08Agencia Estatal de Investigación | Ref. PID2019-107728RB-I0

Removal of Acid Blue 80 from aqueous solutions using chitosan-based beads modified with choline chloride: urea Deep Eutectic Solvent and FeO

An alternative chitosan-based adsorbent modified by impregnation with deep eutectic solvent (DES) choline-chloride:urea at a molar ratio 1:2 proved efficient removal of the anthraquinone dye Acid Blue 80 (AB80) from aqueous solutions, and offered enhanced adsorption capacity compared to the starting materials. The adsorption was mainly affected by initial AB80 concentration, adsorbent dosage, contact time, and slightly influenced by temperature (25–45 °C), and pH (3.5–10). The pseudo-second-order kinetic model fitted the experimental data, and pseudo-first order model fitted as well at the highest AB80 concentration, 250 mg/L. The experimental data agreed with the Langmuir isotherm model, with a maximum adsorption capacity of 61.64 mg/g at 35 °C. The process was exothermic above 100 mg/L of dye and spontaneous up to 200 mg/L (T < 35 °C). The adsorbent could be reused without further treatment at least 5 times providing ≥40% removal, whereas the dye could be efficiently recovered by NaOH desorption. Electrostatic interactions as well as physisorption could explain the adsorption behaviorAgencia Estatal de Investigación | Ref. PID2019-107728RB-I00Xunta de Galicia | Ref. ED431B 2020/08Financiado para publicación en acceso aberto: Universidade de Vigo/CISU

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

With cancer as one of the leading causes of death worldwide, there is a need for the development of accurate, cost-effective, easy-to-use, and fast drug-testing assays. While the NCI 60 cell-line screening as the gold standard is based on a colorimetric assay, monitoring cells electrically constitutes a label-free and non-invasive tool to assess the cytotoxic effects of a chemotherapeutic treatment on cancer cells. For decades, impedance-based cellular assays extensively investigated various cell characteristics affected by drug treatment but lack spatiotemporal resolution. With progress in microelectrode fabrication, high-density Complementary Metal Oxide Semiconductor (CMOS)-based microelectrode arrays (MEAs) with subcellular resolution and time-continuous recording capability emerged as a potent alternative. In this article, we present a new cell adhesion noise (CAN)-based electrical imaging technique to expand CMOS MEA cell-biology applications: CAN spectroscopy enables drug screening quantification with single-cell spatial resolution. The chemotherapeutic agent 5-Fluorouracil exerts a cytotoxic effect on colorectal cancer (CRC) cells hampering cell proliferation and lowering cell viability. For proof-of-concept, we found sufficient accuracy and reproducibility for CAN spectroscopy compared to a commercially available standard colorimetric biological assay. This label-free, non-invasive, and fast electrical imaging technique complements standardized cancer screening methods with significant advances over established impedance-based approaches

Comparative analysis of capture methods for genomic profiling of circulating tumor cells in colorectal cancer

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGThe genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. Here, we contrasted the genomic profiles of CTC pools recovered from metastatic colorectal cancer (mCRC) patients using different enrichment strategies (CellSearch, Parsortix, and FACS). Mutations inferred in the CTC pools differed depending on the enrichment strategy and, in all cases, represented a subset of the mutations detected in the matched primary tumor samples. However, the CTC pools from Parsortix, and in part, CellSearch, showed diversity estimates, mutational signatures, and drug-suitability scores remarkably close to those found in matching primary tumor samples. In addition, FACS CTC pools were enriched in apparent sequencing artifacts, leading to much higher genomic diversity estimates. Our results highlight the utility of CTCs to assess the genomic heterogeneity of individual tumors and help clinicians prioritize drugs in mCRC.Agencia Estatal de Investigación | Ref. PID2019-106247GB-I00Xunta de Galicia | Ref. ED481A-2018/303Instituto de Salud Carlos III | Ref. PI17/00837Instituto de Salud Carlos III | Ref. PI21/01771Axencia Galega de Innovación | Ref. N607B-2020/02Axencia Galega de Innovación | Ref. IN853B 2018/0

Clonality and timing of relapsing colorectal cancer metastasis revealed through whole-genome single-cell sequencing

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGRecurrence of tumor cells following local and systemic therapy is a significant hurdle in cancer. Most patients with metastatic colorectal cancer (mCRC) will relapse, despite resection of the metastatic lesions. A better understanding of the evolutionary history of recurrent lesions is required to identify the spatial and temporal patterns of metastatic progression and expose the genetic and evolutionary determinants of therapeutic resistance. With this goal in mind, here we leveraged a unique single-cell whole-genome sequencing dataset from recurrent hepatic lesions of an mCRC patient. Our phylogenetic analysis confirms that the treatment induced a severe demographic bottleneck in the liver metastasis but also that a previously diverged lineage survived this surgery, possibly after migration to a different site in the liver. This lineage evolved very slowly for two years under adjuvant drug therapy and diversified again in a very short period. We identified several non-silent mutations specific to this lineage and inferred a substantial contribution of chemotherapy to the overall, genome-wide mutational burden. All in all, our study suggests that mCRC subclones can migrate locally and evade resection, keep evolving despite rounds of chemotherapy, and re-expand explosively.Ministerio de Ciencia e Innovación | Ref. PID2019-106247GB-I00AXA Research FundAsociación Española Contra el CáncerXunta de Galicia | Ref. ED481A-2018/30

Association of Rhinitis With Asthma Prevalence and Severity

Multicenter study[Abstract] Asthma and rhinitis often co-exist in the same patient. Although some authors observed a higher prevalence and/or greater severity of asthma in patients with rhinitis, this view is not homogeneous and the debate continues. The aim of our study is to describe the prevalence of rhinitis in children and adolescents and to analyse their relationship with the prevalence of asthma. A multicentre study was conducted using the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC). The target population of the study was all those school children aged 6-7 and 13-14 years from 6 of the main health catchment areas of Galicia (1.9 million inhabitants). The schools required were randomly selected, and all children in the targeted age ranges were included. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) between asthma symptoms of the schoolchildren and rhinitis prevalence. The results were adjusted for parental smoking habits, maternal education level, cat and dog exposure, and obesity. A total of 21,420 valid questionnaires were finally obtained. Rhinitis was associated with a significant increase in the prevalence of asthma in both age groups. The highest OR were 11.375 for exercise induced asthma (EIA) for children with recent rhinoconjunctivitis and 9.807 for children with recent rhinitis in 6-7 years old group. The prevalence OR's are higher in EIA and severe asthmatics. Rhinitis in children and adolescents is associated with a higher prevalence and severity of asthma.This work was funded by the Maria Jose Jove Foundatio