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Individuals' perceptions of their food environments are a mediator between exposure to the environment and people's interaction with it. The Nutrition Environment Measures Surveys (NEMS) are valid and reliable measures to assess food environments. In Spain, there is no adapted instrument to measure the perceived obesogenic environment. This article aims to adapt and evaluate the Perceived Nutrition Environment Measures Survey for a Spanish context (NEMS-P-MED). The Spanish version has 32 questions to measure the perception about availability, accessibility and marketing of 3 types of environment: home, shops and restaurants. We assess feasibility, construct validity and internal consistency reliability through a sample of 95 individuals. The internal consistency was acceptable for most items (Cronbach's alpha coefficients range from 0.6 to 0.9), similar to that of the original scale. The NEMS-P-MED has been shown to be valid and, on certain items reliable, and was useful to assess the population's perceptions of the food environment in the home, restaurants and food stores in a Spanish context. Adapting standardized measurement tools to specific contexts to assess the perceived and observed characteristics of food environments may facilitate the development of effective policy interventions to reduce excess weight.

Zinc is an essential micronutrient that plays an important role as a co-factor to several proteins, including zinc-responsive transcription factors. Trichomonas vaginalis is able to survive in the presence of high zinc concentrations in the male urogenital tract. Several genes in T. vaginalis have been shown to respond to changes in zinc concentrations, however, the zinc-dependent mechanism remains undetermined. Recently, we identified in T. vaginalis the zinc finger protein, TvZNF1, which is an ortholog of the mammal metal transcription factor (MTF1). We searched for several of the zinc-responsive genes in T. vaginalis to determine whether if they contain metal response elements (MRE), cis-acting DNA elements that specifically bind MTF1. Six highly conserved over-represented sequence motifs (TvMREs), which share similarity with other eukaryotic MREs, were identified in the zinc-responsive genes in T. vaginalis. We also demonstrated that some of the TvMREs assemble as divalent complexes either as two closely spaced TvMREs or as two overlapping TvMREs forming a palindromic-like sequence: TGCC(N3)GGCA. Electrophoretic mobility shift assays were used to detect the zinc-dependent binding of TvZNF1 and nuclear proteins from T. vaginalis to this specific palindromic motif. Our results support a novel mechanism used by T. vaginalis for the transcriptional regulation of associated zinc-responsive genes through a MTF1/MRE-like system.

Alzheimer disease (AD) is the primary form of dementia that occurs spontaneously in older adults. Interestingly, the epigenetic profile of the cells forming the central nervous system changes during aging and may contribute to the progression of some neurodegenerative diseases such as AD. In this review, we present general insights into relevant epigenetic mechanisms and their relationship with aging and AD. The data suggest that some epigenetic changes during aging could be utilized as biomarkers and target molecules for the prevention and control of AD., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cigarette smoking has been associated with an increase in oxidative stress (OS) and is considered a predisposing factor to chronic noncommunicable diseases, whilst dietary antioxidants has been proposed as an alternative to cope with this oxidative stress. In this study, 20 smokers and 20 non-smokers were studied with the aim of determining their antioxidant status, as well as the ability of an infusion of 23 medicinal plants, to counteract the damage caused by OS. The plasma, red blood cells (RBCs) and polymorphonuclear cells (PBMCs) of both groups were incubated or not with the horchata infusion extract and then the OS markers, genotoxicity, nanostructure of RBCs membrane and genes related to oxidative responses and cellular functionality were evaluated. Up to 33 different compounds, mainly quercetin glycosides, were identified in the extract. A significant deterioration in the antioxidant status in smokers compared to non-smokers was found. The horchata infusion extract improved the nanostructure of RBCs and DNA damage, as well as the activity of the endogenous antioxidant enzymes and markers of oxidative damage to lipid, and proteins in plasma, RBCs and PBMCs in both groups, whilst no significant changes were found in the expression of different genes related to OS response., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Prostate cancer (PCa) is the second cause of cancer related death in North American men. Androgens play an important role in its progression by regulating the expression of several genes including fusion ones that results from structural chromosome rearrangements. TMPRSS2 - ERG is a fusion gene commonly observed in over 50% of PCa tumors, and its expression can be transcriptionally regulated by the androgen receptor (AR) given its androgen responsive elements. TMPRSS2 - ERG could be involved in epithelial-mesenchymal transition (EMT) during tumor development. ERG has been reported as a key transcriptional factor in the AR-ERG-WNT network where five SFRP proteins, structurally similar to WNT ligands and considered to be WNT pathway antagonists, can regulate signaling in the extracellular space  by binding to WNT proteins or Frizzled receptors. It has been shown that over-expression of SFRP1 protein can regulate the transcriptional activity of AR and inhibits the formation of colonies in LNCaP cells. However, the effect of SFRP1 has been controversial since differential effects have been observed depending on its concentration and tissue location. In this study, we explored the role of exogenous SFRP1 protein in cells expressing the TMPRSS2-ERG fusion., Methods: To evaluate the effect of exogenous SFRP1 protein on PCa cells expressing TMPRSS2-ERG, we performed in silico analysis from TCGA cohort, expression assays by RT-qPCR and Western blot, cell viability and cell cycle measurements by cytometry, migration and invasion assays by xCELLigance system and murine xenografts., Results: We demonstrated that SFRP1 protein increased ERG expression by promoting cellular migration in vitro and increasing tumor growth in vivo in PCa cells with the TMPRSS2-ERG fusion., Conclusions: These results suggest the possible role of exogenous SFRP1 protein as a modulator of AR-ERG-WNT signaling network in cells positive to TMPRSS2-ERG. Further, investigation is needed to determine if SFRP1 protein could be a target in against this type of PCa., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

The use of antibodies to identify neuronal receptors, neurotransmitters, cytoskeletal elements or pathologic protein aggregates, ion channels, adhesion molecules or other cell-type specific markers, is common practice in neuroscience. Antibody detection systems are often based on confocal, epifluorescence or brightfield microscopy. Three types of technical issues can interfere with immunolabeling: low abundance of the target protein, low specific affinity of the antibody and/or signal background sometimes related to tissue fixation. Here, giving tribute to Professor Miledi's mentorship, we propose the application of an antibody signal enhancer (ASE) solution based on glycine, hydrogen peroxide and a detergent mix as a simple, low cost, protocol variation that significantly and specifically improves the signal to noise ratio during immunostaining experiments. We describe three new settings in which ASE improves the detection of a variety of antibodies applied on long-time stored non-human primate brain sections, cell culture monolayers and on squamous carcinomas retrieved from cervical cancer patients. The significant improvement of ASE over optimized immunohistochemical protocols used in clinical practice (i.e. cancer detection) combined with its simplicity and low cost makes it an attractive method for biomedical applications., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: To throw light on the under-researched association between socioeconomic position (SEP) and health in Cuba, this study examined SEP gradients in health and their underlying mechanisms among urban Cuban adults aged 18-65., Methods: By applying linear regressions to data from the 2010 National Survey on Risk Factors and Chronic Diseases, the analysis explored the SEP-health gradient along three SEP dimensions - education, occupation, and skin colour - using ten health measures: self-reported health (SRH), general and abdominal obesity, hypertension, high glucose, high cholesterol, high triglycerides, low high-density lipoprotein cholesterol, metabolic syndrome, and cumulative risk factors. Regressions also included behaviours and health-related risk perceptions (tobacco and alcohol consumption, diet, physical activity, and risk-related behaviours). It thus investigated the SEP-health gradient and its underlying mechanisms via both behaviours and health-related risk perceptions., Results: Once controlling for gender, age, marital status, region and provincial dummies, the analysis detected educational gradients in SRH (estimated coefficient [95% CI]: middle-level education = 3.535 [1.329, 5.741], p < 0.01; high-level education = 5.249 [3.050, 7.448], p < 0.01) that are partially explainable by both health-affecting behaviours (tobacco and alcohol consumption, diet, physical and sedentary activity) and risk perceptions. Using objective measures of health, however, it found no SEP-health gradients other than hypertension among people identified as having Black skin color (adjusted for demographic variables, 0.060 [0.018, 0.101], p < 0.01) and high cholesterol among those identified as having Mulatto or Mestizo skin color (adjusted for demographic variables, - 0.066 [- 0.098, - 0.033], p < 0.01)., Conclusions: In terms of objective health measures, the study provides minimal evidence for an SEP-health gradient in Cuba, results primarily attributable to the country's universal healthcare system - which offers full coverage and access and affordable medications - and its highly developed education system.

The function of the tomato K + , Na + /H + antiporter LeNHX4 has been analyzed using 35S-driven gene construct for overexpressing a histagged LeNHX4 protein in Solanum lycopersicum L. Compared to wild-type plants, the expression of LeNHX4 was enhanced in most of plants transformed with a gene construct for LeNHX4 overexpression although some plants showed a decreased LeNHX4 expression. Overexpression of LeNHX4 was associated to an increased fruit size while silencing of this gene was related to a decreased fruit size. We have investigated the effect of LeNHX4 overexpression on fruit production and quality and we have also evaluated salt tolerance in two different overexpression lines by measuring proline, protein and glucose concentrations in tomato leaves grown either under control (0 mM NaCl) or saline (125 mM NaCl) conditions. Plants overexpressing LeNHX4 showed a higher amount of fruits than WT plants and accumulated higher contents of sugars and cations (Na + and K + ). The application of 125 mM NaCl, affected negatively fruit production and quality of WT plants. However the transgenic lines overexpressing LeNXH4 increased fruit quality and yield. In relation to salt tolerance, overexpression lines showed higher levels of leaf proline, glucose and proteins under NaCl treatment. The overexpression of LeNHX4 in tomato plants, improved salinity tolerance and increased fruit yield and quality under both normal and salinity stress conditions.

In this paper, response surface methodology (RSM) designs and an artificial neural network (ANN) are used to obtain the optimal conditions for the oxy-combustion of a corn-rape blend. The ignition temperature ( T e ) and burnout index ( D f ) were selected as the responses to be optimised, while the CO 2 /O 2 molar ratio, the total flow, and the proportion of rape in the blend were chosen as the influencing factors. For the RSM designs, complete, Box-Behnken, and central composite designs were performed to assess the experimental results. By applying the RSM, it was found that the principal effects of the three factors were statistically significant to compute both responses. Only the interactions of the factors on D f were successfully described by the Box-Behnken model, while the complete design model was adequate to describe such interactions on both responses. The central composite design was found to be inadequate to describe the factor interactions. Nevertheless, the three methods predicted the optimal conditions properly, due to the cancellation of net positive and negative errors in the mathematical adjustment. The ANN presented the highest regression coefficient of all methods tested and needed only 20 experiments to reach the best predictions, compared with the 32 experiments needed by the best RSM method. Hence, the ANN was found to be the most efficient model, in terms of good prediction ability and a low resource requirement. Finally, the optimum point was found to be a CO 2 /O 2 molar ratio of 3.3, a total flow of 108 mL/min, and 61% of rape in the biomass blend., Competing Interests: The authors declare no conflict of interest.

Background: Prolonged postoperative ileus (PPOI) represents a frequent complication following colorectal surgery, affecting approximately 10-15% of these patients. The objective of this study was to evaluate the perioperative risk factors for PPOI development in colorectal surgery., Methods: The present systematic review and meta-analysis was conducted in accordance with the PRISMA Statement. PubMed, EMBASE, SciELO, and LILACS databases were searched, without language or time restrictions, from inception until December 2018. The keywords used were: Ileus, colon, colorectal, sigmoid, rectal, postoperative, postoperatory, surgery, risk, factors. The Newcastle-Ottawa scale and the Jadad scale were used for bias assessment, while the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used for quality assessment of evidence on outcome levels., Results: Of the 64 studies included, 42 were evaluated in the meta-analysis, comprising 29,736 patients (51.84% males; mean age 62 years), of whom 2844 (9.56%) developed PPOI. Significant risk factors for PPOI development were: male sex (OR 1.43; 95% CI 1.25-1.63), age (MD 3.17; 95% CI 1.63-4.71), cardiac comorbidities (OR 1.54; 95% CI 1.19-2.00), previous abdominal surgery (OR 1.44; 95% CI 1.19, 1.75), laparotomy (OR 2.47; 95% CI 1.77-3.44), and ostomy creation (OR 1.44; 95% CI 1.04-1.98). Included studies evidenced a moderate heterogeneity. The quality of evidence was regarded as very low-moderate according to the GRADE approach., Conclusions: Multiple factors, including demographic characteristics, past medical history, and surgical approach, may increase the risk of developing PPOI in colorectal surgery patients. The awareness of these will allow a more accurate assessment of PPOI risk in order to take measures to decrease its impact on this population.

During angiogenesis, new vessels emerge from existing endothelial lined vessels to promote the degradation of the vascular basement membrane and remodel the extracellular matrix (ECM), followed by endothelial cell migration, and proliferation and the new generation of matrix components. Matrix metalloproteinases (MMPs) participate in the disruption, tumor neovascularization, and subsequent metastasis while tissue inhibitors of metalloproteinases (TIMPs) downregulate the activity of these MMPs. Then, the angiogenic response can be directly or indirectly mediated by MMPs through the modulation of the balance between pro- and anti-angiogenic factors. This review analyzes recent knowledge on MMPs and their participation in angiogenesis., (Copyright © 2019 Quintero-Fabián, Arreola, Becerril-Villanueva, Torres-Romero, Arana-Argáez, Lara-Riegos, Ramírez-Camacho and Alvarez-Sánchez.)

Background: Haemonchosis is one of the most economically important parasitic diseases affecting small ruminants all over the world. Chemotherapeutic control has several shortcomings (limited anthelmintic arsenal, frequent resistance) and is hardly affordable by many farm economies. A recombinant antigen (rHc23) was shown to induce significant protection in vaccination trials with single dose challenges and different adjuvants., Results: Lambs were vaccinated with 100 μg rHc23/dose + bacterial immunostimulant (BI) (LPS from Escherichia coli + Propionibacterium acnes extract) (days - 2, 0, 7 and 14) and subjected to a trickle infection with two dosages [6x, 1000 infective larvae (L3) or 6x, 2000 L3]. Vaccinated lambs showed a significant antibody response against rHc23 and Haemonchus contortus soluble extract as assessed by ELISA and Western blot (WB). Fecal egg counts (epg) along the experiment of vaccinated and BI treated lambs were significantly reduced. All vaccinated animals showed total egg output and abomasal helminth burdens (median, average) lower than those from unvaccinated or BI-treated animals lambs although differences were not statistically significant., Conclusions: Vaccination with 100 μg rHc23/dose + BI against H.contortus trickle infections apparently induced lower epg values and helminth burdens at the end of the experiment. Intragroup individual variations did not allow to obtain conclusive results and more research is needed including adjuvants and larger groups of animals to validate the potential value of rHc23 as candidate to develop a recombinant vaccine for lambs haemonchosis.

Introduction: Objectives: to analyze the historical development of the Valencian dietary model, establish the relationship between gastronomy and nutrition and explore the role that reclaiming and adapting culinary and gastronomic traditions could play in the promotion of healthy eating. Methods: literature search and content analysis of studies on the subjects under study. Results: traditional Valencian cuisine is characterized by its variety and diversity at local and regional level; however, the extensive use of vegetables in its dishes and recipes renders it unique and was a crucial aspect of the Valencian population's successful food and nutrition transition in the 1960s. Westernization of the Valencian diet and loss of the heritage of the Mediterranean diet in the late 20th century led to a deterioration in the population's nutritional status and the emergence of problems such as overweight and obesity. Faced with this scenario, the modern cuisine spearheaded by the food sector in the Region of Valencia offers an opportunity to reverse this situation, reclaim the region's gastronomic heritage through dialogue between tradition and innovation and help restore healthier eating habits. Conclusions: the culinary grammar of traditional Valencian gastronomy can improve the population's nutrition by providing a healthy, attractive and tasty diet, besides offering a sustainable alternative for production and consumption through its commitment to regional produce.

The rise in obesity prevalence has increased research interest in the obesogenic environment and its influence on excess weight. The aim of the present study was to review and map data collection instruments for obesogenic environments in adults in order to provide an overview of the existing evidence and enable comparisons. Through the scoping review method, different databases and webpages were searched between January 1997 and May 2018. Instruments were included if they targeted adults. The documents were categorised as food environment or built environment. In terms of results, 92 instruments were found: 46 instruments measuring the food environment, 42 measuring the built environment, and 4 that characterised both environments. Numerous diverse instruments have been developed to characterise the obesogenic environment, and some of them have been developed based on existing ones; however, most of them have not been validated and there is very little similarity between them, hindering comparison of the results obtained. In addition, most of them were developed and used in the United States and were written in English. In conclusion, there is a need for a robust instrument, improving or combining existing ones, for use within and across countries, and more sophisticated study designs where the environment is contemplated in an interdisciplinary approach., Competing Interests: The authors declare no conflict of interest.

Trichomonas vaginalis is the etiological agent of human trichomoniasis. Metronidazole has high treatment success rate among trichomoniasis patients. However, metronidazole-resistant T. vaginalis has been reported, contributing in an increasing number of refractory cases. The mechanism of metronidazole resistance in this parasite is still unclear. In the vaginal environment, where the microaerophilic conditions prevail but the iron concentration is constantly fluctuating, the metronidazole resistance profile of T. vaginalis could be altered. In this study, we developed metronidazole-resistant strains of T. vaginalis and evaluate if iron availability is important to the action of the drug. The modulation of iron levels and iron chelation affected the actions of metronidazole both in susceptible and resistant strains. Interestingly, the early resistant strains exhibited minor iron content. The results of transcription analysis in the early resistant strains showed dysregulation in the expression of genes that codified proteins involved in iron transporter, iron-sulfur cluster assemblage, and oxidative stress response, which could not be observed in the late resistant and susceptible strains. Our results indicate that iron content plays an important role in the metronidazole action in T. vaginalis and likely to be related to iron-sulfur proteins involved in metronidazole activation and oxidative stress via Fenton reaction., (© 2018 International Society of Protistologists.)

Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common nonviral sexually transmitted infection worldwide. Although drug treatment is available, unpleasant side effects and increased resistance to the nitroimidazole family have been documented. Hence, there is a need for the identification of new and safe therapeutic agents against T. vaginalis. Antimicrobial activity of anthraquinone compounds has been reported by a number of authors. The genus Morinda is well known for the diversity of anthraquinones with numerous biological activities. A new anthraquinone, lucidin-ω-isopropyl ether, was isolated from the roots of Morinda panamensis Seem. The structure of the compound was determined by 1 H and 13 C Nuclear Magnetic Resonance (NMR) analyses, in addition to comparison with literature reports. Using in vitro susceptibility assay, the half inhibitory concentration (IC 50 ) of lucidin-ω-isopropyl ether for T. vaginalis (1.32 μg/mL) was found similar to that of metronidazole concentration tested (6 μM = 1.03 μg/mL). In addition, this anthraquinone was capable of inhibiting the parasite's ability to kill HeLa cells and decreased proteolytic activity of the proteinase TvMP50 from T. vaginalis. This was associated with the decreased expression of the mp50 gene. These results demonstrate the trichomonicidal potential by lucidin-ω-isopropyl ether. Further action-mode studies are necessary to elucidate the antiparasitic mechanism of this new anthraquinone to develop a more potent antitrichomonal agent., (© 2018 Wiley Periodicals, Inc.)

Transgenic tomato plants (Solanum lycopersicum L. cv. MicroTom) overexpressing both the K + ,Na + /H + antiporter LeNHX2 and the regulatory kinase SlSOS2 were produced by crossing transgenic homozygous lines overexpressing LeNHX2 and SlSOS2. LeNHX2 expression was enhanced in plants overexpressing LeNHX2 but surprisingly even more in plants overexpressing SlSOS2 with and without LeNHX2. All transgenic plants showed better NaCl tolerance than wild type controls and plants overexpressing both LeNHX2 and SlSOS2 grew better under saline conditions than plants overexpressing only one of these genes. Yield related parameters indicated that single and above all double transgenic plants performed significantly better than wild type controls. All transgenic plants produced fruits with a higher K + content than wild-type plants and plants overexpressing SlSOS2 accumulated more Na + in fruits than the rest of the plants when grown with NaCl. Roots, stems and leaves of transgenic plants overexpressing LeNHX2 showed a higher K + content than wild type and single transgenic plants overexpressing SlSOS2. Na + content in stems and leaves of NaCl treated plants was higher in SlSOS2 overexpressing plants than in wild type and LeNHX2 single transgenic plants. All transgenic lines showed a higher leaf relative water content and a higher plant water content and water use efficiency than wild type controls when both were grown in the presence of NaCl. Results in this work indicate that the joint overexpression of LeNHX2 and SlSOS2 improves growth and water status under NaCl stress, affects K + and Na + homeostasis and enhances fruit yield of tomato plants., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Trichomoniasis is a common sexually transmitted infection caused by Trichomonas vaginalis, which actually does not exist a vaccine for control or prevention. Thus, the identification of new and potent immunogens in T. vaginalis, which can contribute to the development of a vaccine against this parasite, is necessary. Therefore, the aim of this work was to evaluate the potential of a recombinant Transient Receptor Potential-like channel of T. vaginalis (TvTRPV), as a promising immunogen in BALB/c mice. First, TvTRPV was cloned and expressed as a recombinant protein in Escherichia coli BL21 cells and purified by nickel affinity. Next, BALB/c mice were immunized and the antibody levels in mice serum and cytokines from the supernatant of macrophages and from co-culture systems were evaluated. Recombinant TvTRPV triggered high levels of specific total IgG in sera from the immunized mice. Also, a statistically significant increase of cytokines: IL-1β, IL-6, and TNF-α after stimulation with the corresponding antigens in vitro, was identified. Moreover, co-cultures using CD4+ T cells from immunized mice were able to identify higher levels of IL-10 and IFN-γ. These results were useful to validate the immunogenicity of TvTRPV in BALB/c mice, where IL-10-IFN-γ-secreting cells could play a role in infection control, supporting the potential of TvTRPV as a promising target for vaccine against T. vaginalis.

MicroRNAs (miRNAs) are small non-coding RNAs that function as negative regulators of gene expression. Recent evidences suggested that host cells miRNAs are involved in the progression of infectious diseases, but its role in amoebiasis remains largely unknown. Here, we reported an unexplored role for miRNAs of human epithelial colon cells during the apoptosis induced by Entamoeba histolytica . We demonstrated for the first time that SW-480 colon cells change their miRNAs profile in response to parasite exposure. Our data showed that virulent E. histolytica trophozoites induced apoptosis of SW-480 colon cells after 45 min interaction, which was associated to caspases-3 and -9 activation. Comprehensive profiling of 667 miRNAs using Taqman Low-Density Arrays showed that 6 and 15 miRNAs were significantly ( FC > 1.5; p < 0.05) modulated in SW-480 cells after 45 and 75 min interaction with parasites, respectively. Remarkably, no significant regulation of the 6-miRNAs signature (miR-526b-5p, miR-150, miR-643, miR-615-5p, miR-525, and miR-409-3p) was found when SW-480 cells were exposed to non-virulent Entamoeba dispar . Moreover, we confirmed that miR-150, miR-643, miR-615-5p, and miR-525 exhibited similar regulation in SW-480 and Caco2 colon cells after 45 min interaction with trophozoites. Exhaustive bioinformatic analysis of the six-miRNAs signature revealed intricate miRNAs-mRNAs co-regulation networks in which the anti-apoptotic XIAP, API5, BCL2, and AKT1 genes were the major targets of the set of six-miRNAs. Of these, we focused in the study of functional relationships between miR-643, upregulated at 45 min interaction, and its predicted target X-linked inhibitor of apoptosis protein (XIAP). Interestingly, interplay of amoeba with SW-480 cells resulted in downregulation of XIAP consistent with apoptosis activation. More importantly, loss of function studies using antagomiRs showed that forced inhibition of miR-643 leads to restoration of XIAP levels and suppression of both apoptosis and caspases-3 and -9 activation. Congruently, mechanistic studies using luciferase reporter assays confirmed that miR-643 exerts a postranscripcional negative regulation of XIAP by targeting its 3'-UTR indicating that it's a downstream effector. In summary, we provide novel lines of evidence suggesting that early-branched eukaryote E. histolytica may promote apoptosis of human colon cells by modulating, in part, the host microRNome which highlight an unexpected role for miRNA-643/XIAP axis in the host cellular response to parasites infection.

Epigenomics refers to the study of genome-wide changes in epigenetic mechanisms including DNA methylation, histone modifications and non-coding RNAs expression. The alterations in normal DNA methylation and histone acetylation/deacetylation patterns lead to deregulated transcription and chromatin organization resulting in altered gene expression profiles that facilitates tumor development and progression. In consequence, novel therapeutic strategies aimed at reversing aberrant epigenetic marks in cancer cells have been developed and used in recent molecular studies and clinical trials. Pharmaco-epigenomics is a research area, which refers to the study of epigenome changes in cancer development and how chemotherapeutic agents can reverse these aberrant epigenetic marks by targeting the epigenetic machinery. Besides, the effects of genome-wide polymorphisms in populations leading to variations in drug response are also study subject of pharmaco-epigenomics and are being studied extensively in cancer. Recent findings showed that drug response could be largely influenced by the presence of aberrant epigenetic marks of the whole genome. This implies that biological pathways and cellular processes are under the impact of epigenome status. However, data about the relationship between drug response and the epigenomic variations is still scarce mainly because the epigenome is highly variable between individuals. The present chapter reviewed the advances on the epigenetics changes mainly DNA methylation and histones modifications on cervical and breast human cancers. A special emphasis in how they could be used as targets for the development and use of novel drugs in cancer therapy is delineated.

The giant squid (Dosidicus gigas) is a species of commercial interest as a source of protein, and it can be developed into ready-to-eat food products, including expanded extrusion snacks (EES). EES are prepared primarily from starch; however, adding animal protein increases the nutritional contents. The objective of this study was to evaluate the effect of the protein-carbohydrate interactions on the physical and morphological characteristics of an EES made of squid mantle and potato-corn flour. The independent variable was the squid mantle content (40, 60, 80, and 100%) and two controls (0 1  = 100% potato, 0 2  = 100% corn). The expansion rate (ER) of the sample is significantly minor (p < .5) when the squid mantle content increases ER = 2.0, 1.8 1.4 to 40, 60, and 80%, respectively. In samples with more protein, crispness and crunchiness were reduced, whereas the hardness increased. Digital imaging analysis indicated that the interaction between protein and starch causes significant morphometric changes to the fractal dimension (2.665-2.739) and lacunarity (0.61-1.29). The results showed that it is possible to incorporate up to 60% squid mantle to prepare EES that possess texture and morphometric characteristics competitive in reported studies with snacks usually incorporating flours, corn, and wheat in the formulations., Practical Applications: The giant squid is a very attractive species because its meat has low caloric intake, high protein content, and is an important source of omega 3 fatty acids. Despite the desirable qualities of the squid meat its consumption is very low due to the low diffusion of the properties of its meat, acid, and ammoniacal flavor, rigid texture that requires prolonged cooking times and lack of alternatives of consumption. In Mexico, this type of squid is mainly destined for export as frozen mantle and products with little added value, which generates little economic benefit. Therefore, the results of this research may be of interest to the squid processing industry, which demands new forms of consumption of this marine species to increase their commercialization and added value., (© 2018 Wiley Periodicals, Inc.)

RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attractive approach in cancer. Here, we uncovered a miR-204 cooperative targeting of multiple signaling transducers involved in vasculogenic mimicry (VM). Our data showed that invasive triple negative MDA-MB-231 and Hs-578T breast cancer cells, but not poorly invasive MCF-7 cells, efficiently undergoes matrix-associated VM under hypoxia. Ectopic restoration of miR-204 in MDA-MB-231 cells leads to a potent inhibition of VM and reduction of number of branch points and patterned 3D channels. Further analysis of activation state of multiple signaling pathways using Phosphorylation Antibody Arrays revealed that miR-204 reduced the expression and phosphorylation levels of 13 proteins involved in PI3K/AKT, RAF1/MAPK, VEGF, and FAK/SRC signaling. In agreement with phospho-proteomic profiling, VM was impaired following pharmacological administration of PI3K and SRC inhibitors. Mechanistic studies confirmed that miR-204 exerts a negative post-transcriptional regulation of PI3K-α and c-SRC proto-oncogenes. Moreover, overall survival analysis of a large cohort of breast cancer patients indicates that low miR-204 and high FAK/SRC levels were associated with worst outcomes. In conclusion, our study provides novel lines of evidence indicating that miR-204 may exerts a fine-tuning regulation of the synergistic transduction of PI3K/AKT/FAK mediators critical in VM formation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Previously, metalloproteinase was isolated and identified from Trichomonas vaginalis, belonging to the aminopeptidase P-like metalloproteinase subfamily A/B, family M24 of clan MG, named TvMP50. The native and recombinant TvMP50 showed proteolytic activity, determined by gelatin zymogram, and a 50 kDa band, suggesting that TvMP50 is a monomeric active enzyme. This was an unexpected finding since other Xaa-Pro aminopeptidases/prolidases are active as a biological unit formed by dimers/tetramers. In this study, the evolutionary history of TvMP50 and the preliminary crystal structure of the recombinant enzyme determined at 3.4 Å resolution is reported. TvMP50 was shown to be a type of putative, eukaryotic, monomeric aminopeptidase P, and the crystallographic coordinates showed a monomer on a "pseudo-homodimer" array on the asymmetric unit that resembles the quaternary structure of the M24B dimeric family and suggests a homodimeric aminopeptidase P-like enzyme as a likely ancestor. Interestingly, TvMP50 had a modified N-terminal region compared with other Xaa-Pro aminopeptidases/prolidases with three-dimensional structures; however, the formation of the standard dimer is structurally unstable in aqueous solution, and a comparably reduced number of hydrogen bridges and lack of saline bridges were found between subunits A/B, which could explain why TvMP50 portrays monomeric functionality. Additionally, we found that the Parabasalia group contains two protein lineages with a "pita bread" fold; the ancestral monomeric group 1 was probably derived from an ancestral dimeric aminopeptidase P-type enzyme, and group 2 has a probable dimeric kind of ancestral eukaryotic prolidase lineage. The implications of such hypotheses are also presented.

Background: Polyparasitism is the rule in all animal species, including humans, and has an important role in pathogenicity, diagnosis and control measures. Among them, co-infections by gastrointestinal helminths and protists are very prevalent under natural conditions but experimental infections are relatively scarce. Thus, despite the frequent association of visceral Leishmania infections and intestinal helminth parasitism the experimental co-infection has not been addressed. Heligmosomoides polygyrus, an intestinal nematode of mice, is related to other helminths causing important pathologies and is a model species for immunological studies. Mice are valuable experimental model for visceral leishmaniasis., Methods: BALB/c mice infected with H. polygyrus (200 third-stage larvae, L3) were subsequently infected seven days later with Leishmania infantum (10 7 promastigotes) with the aim of determining the effect of the overinfection on the host response to the primary infection with the helminth., Results: Overinfection with the protist did not affect the establishment rate of the nematode but induced a higher fecal egg output. Helminth burdens in co-infected animals were significant at the end of the experiment. Early unspecific immune suppression induced by the nematode in mesenteric lymph nodes was not switched by L. infantum infection. Co-infection elicited a higher serum antibody (IgG 1 ) response against the helminth., Conclusions: Visceral leishmanial overinfection aggravated the early host response against primary infections with the intestinal helminth. This effect was evidenced by an increased longevity and higher production of non-protective antibodies.

Murine leprosy, caused by Mycobacterium lepraemurium (MLM), is a chronic disease that closely resembles human leprosy. Even though this disease does not directly involve the nervous system, we investigated a possible effect on working memory during this chronic infection in Balb/c mice. We evaluated alterations in the dorsal region of the hippocampus and measured peripheral levels of cytokines at 40, 80, and 120 days post-infection. To evaluate working memory, we used the T-maze while a morphometric analysis was conducted in the hippocampus regions CA1, CA2, CA3, and dentate gyrus (DG) to measure morphological changes. In addition, a neurochemical analysis was performed by HPLC. Our results show that, at 40 days post-infection, there was an increase in the bacillary load in the liver and spleen associated to increased levels of IL-4, working memory deterioration, and changes in hippocampal morphology, including degeneration in the four subregions analyzed. Also, we found a decrease in neurotransmitter levels at the same time of infection. Although MLM does not directly infect the nervous system, these findings suggest a possible functional link between the immune system and the central nervous system.

Introduction: the stage of autarky and early years of developmentalism was one of the periods in the contemporary history of Spain when inequalities in food and nutrition became more pronounced., Objectives: to examine malnutrition among the rural population (municipalities with fewer than 2000 inhabitants), including territorial inequalities and the delayed onset of a rural food and nutrition transition., Methods: we analysed the rural food and nutrition surveys carried out by the General Commission for Supplies and Transport (Spanish initials: CAT) and the Food and Nutrition Education Programme (Spanish initials: EDALNU) between 1964 and 1972., Results: the rural population presented a deficit of animal proteins, calcium and vitamins A and B2, due to scant consumption of protective foods. Andalucía and inland Spain were the regions with the highest percentage of people whose diet did not meet nutritional requirements. These deficiencies were not only responsible for the prevalence of caries and skin, mucous membrane and eye lesions, but were also behind delayed growth (height and weight). This was not the result so much of poverty as of the persistence of poor eating habits., Conclusions: besides evidencing the delayed onset of a food and nutritional transition in the Spanish rural population, our findings document policies that sought to encourage the consumption of protective foods in rural areas and empower the population with regard to food and nutrition.

Infection with Trichomonas vaginalis produces a malodorous seropurulent vaginal discharge due to several chemicals, including polyamines. The presence of 1,4-diamino-2-butanone (DAB) reduces the amount of intracellular putrescine by 90%, preventing the cotransport of exogenous spermine. DAB-treated parasites present morphological changes, which are restored by adding exogenous putrescine into the culture medium. However, the effect of polyamines over the trichomonad proteomic profile is unknown. In this study, we used a proteomic approach to analyze the polyamine-depletion and restoration effect by exogenous putrescine on T. vaginalis proteome. In the presence of inhibitor DAB, we obtained 369 spots in polyamine-depleted condition and observed 499 spots in the normal culture media. With DAB treatment, the intensity of 43 spots was increased but was found to be reduced in 39 spots, as compared to normal conditions. Interestingly, in DAB-treated parasites restored with a medium with added exogenous putrescine, 472 spots were found, of which 33 were upregulated and 63 were downregulated in protein intensity. Some of these downregulated proteins in DAB-treated parasites are involved in several cellular pathways such as glycolysis, glycolytic fermentation, arginine dihydrolase pathway, redox homeostasis, host cell binding mediated by carbohydrate, chaperone function, and cytoskeletal remodeling. Interestingly, the intensity of some of the proteins was restored by adding exogenous putrescine. In conclusion, the presence of DAB altered the proteomic profile of T. vaginalis, resulting in a decrease in the intensity of 130 proteins and an increase in the intensity of 43 proteins that was restored by the addition of putrescine.

Haemonchus contortus is the most pathogenic gastrointestinal helminth of small ruminants. Natural or experimental repeated infections and several native antigens confer a partially protective immune response but vaccination with subunit antigens has been elusive. Promising results have been obtained with a recombinant form of a somatic antigen (rHc23). In this paper we present the results obtained in vaccination trials in lambs using two dosages of rHc23 and standard adjuvants. Six-months old Manchego females lambs were vaccinated with rHc23 (50 or 200 μg/dose) adjuvanted with 1mL aluminum hydroxide on days -42, -28 and -14 or with 200 μg/dose rHc23 and 5 mg Quil A on days -49, -28 and -7. Control lambs were kept receiving only the adjuvants the same days or no treatment. Moreover one group did not receive any treatment or infection. On day 0 vaccinated lambs, untreated animals and those receiving the adjuvant were infected per os with a monospecific single infection of 4000 L3 of H. contortus. Infection was kept for 58 days and follow-up included the determination of serum specific antibody response (ELISA, WB), hematological parameters (eosinophil counts, hematocrit) and fecal egg counts (epg). Absence of hematocrit alterations, reduction of helminth's eggs output and abomasal parasite burden at the end of the experiment were the efficacy criteria of vaccination with the recombinant. Immunization with both adjuvants and antigen dosages elicited strong antibody responses particularly with Quil A. Vaccinated groups showed significant reduction of fecal egg excretion and abomasal helminth burdens. Highest protection of lambs against challenge was achieved with aluminum hydroxide and 200 μg/dose rHc23 with a reduction of over 70% of the abomasal burden and over 80% of fecal egg output. Results suggest that rHc23 could be a valuable recombinant candidate for vaccination against haemonchosis. No clear relationship was found between antibody levels and protection this pointing towards involvement of both humoral and cellular components in the protective response elicited by rHc23.

In our country, it is estimated that about 40% of the female population are physically and/or mentally abused by their partners, and between 21% and 60% of those women develop post-traumatic stress disorder. In this population, the knowledge about coping strategies is limited., Objectives: Identify whether signifcant differences exist as regards coping behaviors used in victims of gender violence between those women who develop post-traumatic stress disorder and those who do not., Methods: The study involved 30 women who received an informed consent, a sociodemographic questionnaire, the questionnaire of the coping responses inventory CRI-A and the SCID-I., Results: There were statistically signifcant differences regarding the use of logical analysis, seeking guidance and support, cognitive avoidance, and acceptance-resignation, used more by the post-traumatic stress disorder group; and minor use of positive reappraisal, problem solving and emotional discharge., Discussion: Coping strategies of positive revaluation, problem solving and emotional discharge have been related to the decrease in the severity of depressive and anxious symptomatology. On the other hand, the usage of Cognitive Avoidance has been related to the increase in anxious and depressive symptomatology.

Using two waves of the National Survey on Risk Factors and Chronic Diseases in Cuba, we identify demographic and socioeconomic characteristics associated with obesity among urban adults aged 18+ and decompose the change in obesity within this 9-year period using both the mean-based Blinder-Oaxaca decomposition and a nonlinear approach. Our results reveal significant increases in overweight and obesity (2.3, 3.1, and 7.6 percentage points for BMI-based overweight, BMI-based obesity, and abdominal obesity, respectively). Depending on the decompositional approach and obesity measure, our analysis explains between 13% and 51% of the rise in overweight and obesity, with most part attributable to changes in risky behavior, age, and education. Of particular importance are the large decline in smoking and the population's changing age structure., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Intralymphatic histiocytosis is a benign condition characterized by poorly defined erythematous plaques (sometimes forming a reticular pattern) as well as the presence of nodules and vesicles. Its etiology and pathogenesis appear to be related to chronic inflammation in the affected area, prior surgery, or systemic disease, particularly rheumatoid arthritis. We report on 2 new cases, both associated with joint surgery in the affected area and osteoarticular disease (primary synovial osteochondromatosis and rheumatoid arthritis). This is a chronic disease and there is no specific treatment. Different treatment options were chosen in the 2 cases described. A spectacular response to treatment with oral pentoxifylline and topical tacrolimus was observed in 1 of the patients., (Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

The aim of this volume is to encourage the use of systems-level methodologies to contribute to the improvement of human-health . We intend to motivate biomedical researchers to complement their current theoretical and empirical practice with up-to-date systems biology conceptual approaches. Our perspective is based on the deep understanding of the key biomolecular regulatory mechanisms that underlie health, as well as the emergence and progression of human-disease . We strongly believe that the contemporary systems biology perspective opens the door to the effective development of novel methodologies to the improvement of prevention . This requires a deeper and integrative understanding of the involved underlying systems-level mechanisms. In order to explain our proposal in a simple way, in this chapter we privilege the conceptual exposition of our chosen framework over formal considerations. The formal exposition of our proposal will be expanded and discussed later in the next chapters.

The aim of this chapter is to illustrate the modeling procedures discussed in the previous chapter via three well-chosen examples.

Being concerned by the understanding of the mechanism underlying chronic degenerative diseases , we presented in the previous chapter the medical systems biology conceptual framework that we present for that purpose in this volume. More specifically, we argued there the clear advantages offered by a state-space perspective when applied to the systems-level description of the biomolecular machinery that regulates complex degenerative diseases. We also discussed the importance of the dynamical interplay between the risk factors and the network of interdependencies that characterizes the biochemical, cellular, and tissue-level biomolecular reactions that underlie the physiological processes in health and disease. As we pointed out in the previous chapter, the understanding of this interplay (articulated around cellular phenotypic plasticity properties, regulated by specific kinds of gene regulatory networks) is necessary if prevention is chosen as the human-health improvement strategy (potentially involving the modulation of the patient's lifestyle). In this chapter we provide the medical systems biology mathematical and computational modeling tools required for this task.

The zinc fingers proteins (ZNF) are the largest family of DNA binding proteins and can act as transcriptional factors in eukaryotes. ZNF are implicated in activation in response to environmental stimulus by biometals such as Zn 2+ . Many of these proteins have the classical C 2 H 2 zinc finger motifs (C 2 H 2 -ZNFm) of approximately 30 amino acids, where a Zn 2+ ion is coordinated by two cysteine and two histidine residues. Trichomonas vaginalis is a protozoan parasite than responds to environmental changes including Zn 2+ . Until now has not been described any ZNF that could be involved in the regulation of genic expression of T. vaginalis. Here, we characterized in silico and experimentally an annoted ZNF (TvZNF1) from T. vaginalis and isolated the gene, tvznf1 encoding it. TvZNF1 have eight C 2 H 2 -ZNFm with residues that maybe involved in the structural stability of DNA binding motifs. In this work we confirmed the Zn 2+ upregulation expression of tvznf1 gene. Recombinant TvZNF1 was able to bind to specific DNA sequences according to EMSA assay. Additionally, we demonstrated that recombinant TvZNF1 bind to MRE signature in vitro, which strongly suggests its role in transcriptional regulation, similar to the one observed for mammalian MTF-1. This result suggested a conserved mechanism of genic regulation mediated by ZNFs in T. vaginalis.

Background: Bovine babesiosis is a tick-borne disease caused by the protozoan parasites of the genus Babesia. In their host vector, Babesia spp. undergo sexual reproduction. Therefore, the development of sexual stages and the subsequent formation of the zygote are essential for the parasite to invade the intestinal cells of the vector tick and continue its life-cycle. HAP2/GCS1 is a protein identified in plants, protozoan parasites and other organisms that has an important role during membrane fusion in fertilization processes. The identification and characterization of HAP-2 protein in Babesia would be very significant to understand the biology of the parasite and to develop a transmission-blocking vaccine in the future., Results: To isolate and sequence the hap2 gene DNA from an infected bovine with Babesia bigemina was purified. The hap2 gene was amplified, cloned and sequenced. The sequences of hap2 from four geographically different strains showed high conservation at the amino acid level, including the typical structure with a signal peptide and the HAP2/GSC domain. Antisera anti-HAP2 against the conserved extracellular region of the HAP2 amino acid sequence were obtained from rabbits. The expression of hap2 in the host and vector tissues was analyzed by using semi-quantitative RT-PCR, and the protein was examined by western blot and immunofluorescence. Based on the RT-PCR and WB results, HAP2 is expressed in both, sexual stages induced in vitro, and in infected ticks as well. We did not detect any expression in asexual erythrocytic stages of B. bigemina, relevantly anti-HAP2 specific antibodies were able to block zygotes formation in vitro., Conclusion: Babesia bigemina HAP2 is expressed only in tick-infecting stages, and specific antibodies block zygote formation. Further studies regarding the function of HAP2 during tick infection may provide new insights into the molecular mechanisms of sexual reproduction of the parasite.

Introduction: Short chain fatty acids contain up to 6 carbon atoms. Among them, butyric acid stands out for its key role in pathologies with intestinal affectation. Butyric acid is the main energetic substrate of the colonocyte, it stimulates the absorption of sodium and water in the colon, and presents trophic action on the intestinal cells., Objectives: To review the clinical use of formulations for the oral use of butyric acid., Methods: Review of published articles on oral supplementation with butyric acid in intestinal pathologies., Results: The publications mainly deal with the use of oral butyric acid in pathologies involving inflammation and / or alterations of intestinal motility. Highlighting the clinical potential in inflammatory bowel diseases and irritable bowel syndrome., Conclusion: The use of oral supplementation with butyric acid is a promising strategy in pathologies such as inflammatory bowel diseases and irritable bowel syndrome. Bio-available butyric acid formulations with acceptable organoleptic characteristics are being advanced.

Trace elements such as Zinc and Iron are essential components of metalloproteins and serve as cofactors or structural elements for enzymes involved in several important biological processes in almost all organisms. Because either excess or insufficient levels of Zn and Fe can be harmful for the cells, the homeostatic levels of these trace minerals must be tightly regulated. The Zinc regulated transporter, Iron regulated transporter-like Proteins (ZIP) comprise a diverse family, with several paralogues in diverse organisms and are considered essential for the Zn and Fe uptake and homeostasis. Zn and Fe has been shown to regulate expression of proteins involved in metabolism and pathogenicity mechanisms in the protozoan pathogen Trichomonas vaginalis, in contrast high concentrations of these elements were also found to be toxic for T. vaginalis trophozoites. Nevertheless, Zn and Fe uptake and homeostasis mechanisms is not yet clear in this parasite. We performed a genome-wide analysis and localized the 8 members of the ZIP gene family in T. vaginalis (TvZIP1-8). The bioinformatic programs predicted that the TvZIP proteins are highly conserved and show similar properties to the reported in other ZIP orthologues. The expression patterns of TvZIP1, 3, 5 and 7 were diminished in presence of Zinc, while the rest of the TvZIP genes showed an unchanged profile in this condition. In addition, TvZIP2 and TvZIP4 showed a differential expression pattern in trophozoites growth under different Iron conditions. These results suggest that TvZIP genes encode membrane transporters that may be responsible for the Zn and Fe acquisition in T. vaginalis.

Trichomonas vaginalis is a protozoan parasite that can adapt to the trichomonicidal Zn 2+ concentrations of the male urogenital tract microenvironment. This adaptation is mediated by molecular mechanisms, including proteinase expression, that are regulated by cations such as Zn 2+ . Herein, we characterized the previously identified 50kDa metalloproteinase aminopeptidase P (M24 family) member TvMP50 as a new Zn 2+ -mediated parasite virulence factor. Quantitative RT-PCR and indirect immunofluorescence assays corroborated the positive regulation of both mp50 gene expression and native TvMP50 protein overexpression in the cytoplasm and secretion products of parasites grown in the presence of Zn 2+ . Furthermore, this active metalloproteinase was characterized as a new virulence factor by assaying cytotoxicity toward prostatic DU145 cell monolayers as well as the inhibition of parasite and secreted soluble protein proteolytic activity in the 50kDa proteolytic region by the specific metalloproteinase inhibitor 1,10-phenanthroline and the chelating agents EDTA and EGTA. Parasite and secreted soluble protein cytotoxicity toward DU145 cells were reduced by treatment with an α-rTvMP50 polyclonal antibody. Our results show that the metalloproteinase TvMP50 is a new virulence factor modulated by Zn 2+ , which is present during male trichomoniasis, possibly explaining T. vaginalis survival even within the adverse conditions of the male urogenital microenvironment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis., Methods: We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways., Results: The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism., Conclusion: Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further explored in preeclampsia pathogenesis through experimental approaches.

Food and nutrition education is an essential tool to ensure public health. The year 1961 saw the launch of the Food and Nutrition Education Programme (EDALNU), which helped Spanish population to complete their nutrition transition. The aim of this study was to analyze the characteristics of the health education network which was created as part of the program. A total of 46,752 people, 94% of whom were women, received training on food and nutrition. Of these, 89.54% obtained the basic certificate, and 8.80% were awarded the diploma. Some 1,407 courses were given, reaching a peak in 1979 with 131 courses and 4,029 students. The most active provinces were Madrid, with 26.65% of the courses; Valencia, with 7.60%; Murcia, with 7.53%, and Malaga, with 6.75%. The Spanish Ministry of Culture and Education organized the largest number of courses (26.23%), followed by the Women’s Section (11.16%) and Catholic Action (5.12%). Diploma courses were taught for 160 hours, while basic courses lasted 40 hours. The training delivered was affected by changes in the EDALNU program and the Spanish administrative and political structure. Our research revealed that the development and gender balance of the network of trainers presented regional inequalities, and that a wide range of institutions were involved in delivering the courses

This paper presents the problem of safe and fast transportation of packages by an Unmanned Aerial Vehicle (UAV) kind quadrotor. A mathematical model and a control strategy for a special class of underactuated mechanical systems, composed of a quadrotor transporting a cable-suspended payload, are proposed. The Euler-Lagrange formulation is used to obtain the dynamic model of the system, where the integrated dynamics of the quadrotor, cable and payload are considered. An Interconnection and Damping Assignment-Passivity Based Control (IDA-PBC) is chosen because of its inherent robustness against parametric uncertainty and unmodeled dynamics. Two cases are considered to obtain two different control laws, in the first case, the designed control law depends on the swing angle of the payload, in the second case the control law does not depend on it. The control objective is to transport the payload from point to point, with swing reduction along trajectory. Experimental results using monocular vision based navigation are shown to evaluate the proposed control law., (Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.)

Molecular regulation was initially assumed to follow both a unidirectional and a hierarchical organization forming pathways. Regulatory processes, however, form highly interlinked networks with non-hierarchical and non-unidirectional structures that contain statistically overrepresented circuits or motifs. Here, we analyze the behavior of pathways containing non-unidirectional (i.e. bidirectional) and non-hierarchical interactions that create motifs. In comparison with unidirectional and hierarchical pathways, our pathways have a high diversity of behaviors, characterized by the size and number of attractors. Motifs have been studied individually showing that feedback circuit motifs regulate the number and size of attractors. It is less clear what happens in molecular networks that usually contain multiple feedbacks. Here, we find that the way feedback circuits couple to each other (i.e., the combination of the functionalities of feedback circuits) regulate both the number and size of the attractors. We show that the different expected results of epistasis analysis (a method to infer regulatory interactions) are produced by many non-hierarchical and non-unidirectional structures. Thus, these structures cannot be correctly inferred by epistasis analysis. Finally, we show that the combinations of functionalities, combined with other network properties, allow for a better characterization of regulatory structures., Competing Interests: The authors declare no competing financial interests.

Purpose: To report a case of choroidal effusion probably caused by angiotensin receptor II blocker., Case Report: A 52-year-old man with aplastic anemia and high blood pressure who developed unilateral acute angle closure glaucoma after receiving oral cyclosporine and angiotensin II receptor blocker (losartan). Ophthalmic examination revealed visual acuity of 20/30 in the left eye, mild mydriasis, iris bombe, no anterior chamber reaction, mild conjunctival hyperemia, and the intraocular pressure of 30 mmHg. After laser YAG iridotomy, funduscopy was performed showing a choroidal circumscribed lesion at the inferotemporal quadrant. Diagnostic tests ruled out any inflammatory or malignancy process, and the choroidal lesion spontaneously disappeared. After 20 months of follow-up, patient's ocular remained stable., Conclusion: This is the third case of choroidal effusion associated with angiotensin II receptor blockers. Since idiosyncratic ciliochoroidal effusion is a diagnosis of exclusion, it is mandatory to rule out more frequent causes, such as inflammatory or malignant processes., Competing Interests: There are no conflicts of interest.