Scope
Some polyphenol‐derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. ...Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly‐diagnosed BC patients and the tissue‐occurring metabolites’ anticancer activity are evaluated.
Methods and results
Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy‐confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC‐QTOF‐MS using targeted metabolomics. Anticancer activity was tested in MCF‐7 and MDA‐MB‐231 BC cells. Mainly phase‐II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L–1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L–1 in NT and MT, respectively). Breast tissue‐occurring metabolites’ antiproliferation was mainly exerted in p53‐wild‐type MCF‐7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone‐derived metabolites exerted estrogenic‐like activity.
Conclusion
Curcuminoids could be coadjuvants that might help fight BC upon regular consumption.
A total of 47 curcuminoid, isoflavone, resveratrol, and lignan‐derived metabolites, mostly conjugated, were detected in malignant mammary tissues of breast cancer patients. However, free curcumin, but not its glucuronide, was detected at micromolar concentration, likely due to a glucuronidation‐saturation process. Breast tissue‐occurring metabolites, mainly, curcuminoids, induced cell cycle arrest, senescence, and apoptosis via p53/p21, while isoflavone metabolites exerted estrogenic activity.
•This study has identified the 13 most vulnerable countries in terms of tourism competitiveness.•The most vulnerable are Panama, Georgia, Bahrain, Morocco, Montenegro, Albania, Mexico, Dominican ...Republic, Jordan, Tunisia, Cape Verde, Honduras, and Lebanon.•The keys dimensions that condition the competitiveness have been identified.•These dimensions are related to cultural heritage, protection of natural areas, information and communication technologies, among others.
Business activities within the tourism industry are especially suffering from the consequences of the COVID19 pandemic. Those countries whose economy depends largely on tourism will experience a troublesome situation for years to come. Their return to a normal situation will be conditioned by the competitiveness of their tourism sector. The study begins by pinpointing the countries that have been more hardly stricken by the pandemic and in which tourism accounts for a greater share of the GDP. A comparative analysis of the competitiveness of these countries with that of world-leading countries will be carried out so as to conclude which will face the recovery period in a more vulnerable situation. The measurement of tourism competitiveness will be supported by the creation of a synthetic indicator based on the P2 distance method. A group of 13 countries has been identified as the most vulnerable, and it is advisable to act urgently in the following areas: the promotion of cultural elements and the historical and artistic heritage, the protection of natural areas, the availability of information and communication technologies, the international openness of the destination, and the availability of transportation infrastructures and tourist services.
Tourism is a key sector in the sustainable development of rural environments. Its ability to create stable employment and an acceptable level of profits is conditioned by the stability of tourist ...activity throughout the year. This paper compares the level of seasonality of a group of rural destinations to that of coastal and urban destinations. By doing so, we intend to determine whether seasonality-related problems exist in the rural environment or not. The second aim is related to the first one: the proposal of a new, more comprehensive and objective methodology that can measure the intensity of seasonality based on a DP2 synthetic indicator. The DP2 indicator groups information about different representative variables of seasonality. The study takes the main tourist spots in Spain as a reference. The analysis concludes that the annual level of stability of rural tourism is not far from the stability of urban tourism, which is the most stable, as seasonality is much higher in coastal destinations. The methodology that provides the framework to build the DP2 indicator has allowed us to identify which variables explain the differences in the level of seasonality of each destination to a large extent. The results showed that the variables that do so are related to the internalization of the destination and changes in the availability of bed places.
Thermal diodes--devices that allow heat to flow preferentially in one direction--are one of the key tools for the implementation of solid-state thermal circuits. These would find application in many ...fields of nanoscience, including cooling, energy harvesting, thermal isolation, radiation detection and quantum information, or in emerging fields such as phononics and coherent caloritronics. However, both in terms of phononic and electronic heat conduction (the latter being the focus of this work), their experimental realization remains very challenging. A highly efficient thermal diode should provide a difference of at least one order of magnitude between the heat current transmitted in the forward temperature (T) bias configuration (Jfw) and that generated with T-bias reversal (Jrev), leading to ℛ = Jfw/Jrev ≫ 1 or ≪ 1. So far, ℛ ≈ 1.07-1.4 has been reported in phononic devices, and ℛ ≈ 1.1 has been obtained with a quantum-dot electronic thermal rectifier at cryogenic temperatures. Here, we show that unprecedentedly high ratios of ℛ ≈ 140 can be achieved in a hybrid device combining normal metals tunnel-coupled to superconductors. Our approach provides a high-performance realization of a thermal diode for electronic heat current that could be successfully implemented in true low-temperature solid-state thermal circuits.
Single-nucleotide polymorphisms (SNPs) are the most abundant type of DNA sequence polymorphisms. Their higher availability and stability when compared to simple sequence repeats (SSRs) provide ...enhanced possibilities for genetic and breeding applications such as cultivar identification, construction of genetic maps, the assessment of genetic diversity, the detection of genotype/phenotype associations, or marker-assisted breeding. In addition, the efficiency of these activities can be improved thanks to the ease with which SNP genotyping can be automated. Expressed sequence tags (EST) sequencing projects in grapevine are allowing for the in silico detection of multiple putative sequence polymorphisms within and among a reduced number of cultivars. In parallel, the sequence of the grapevine cultivar Pinot Noir is also providing thousands of polymorphisms present in this highly heterozygous genome. Still the general application of those SNPs requires further validation since their use could be restricted to those specific genotypes.
In order to develop a large SNP set of wide application in grapevine we followed a systematic re-sequencing approach in a group of 11 grape genotypes corresponding to ancient unrelated cultivars as well as wild plants. Using this approach, we have sequenced 230 gene fragments, what represents the analysis of over 1 Mb of grape DNA sequence. This analysis has allowed the discovery of 1573 SNPs with an average of one SNP every 64 bp (one SNP every 47 bp in non-coding regions and every 69 bp in coding regions). Nucleotide diversity in grape (pi = 0.0051) was found to be similar to values observed in highly polymorphic plant species such as maize. The average number of haplotypes per gene sequence was estimated as six, with three haplotypes representing over 83% of the analyzed sequences. Short-range linkage disequilibrium (LD) studies within the analyzed sequences indicate the existence of a rapid decay of LD within the selected grapevine genotypes. To validate the use of the detected polymorphisms in genetic mapping, cultivar identification and genetic diversity studies we have used the SNPlextrade mark genotyping technology in a sample of grapevine genotypes and segregating progenies.
These results provide accurate values for nucleotide diversity in coding sequences and a first estimate of short-range LD in grapevine. Using SNPlextrade mark genotyping we have shown the application of a set of discovered SNPs as molecular markers for cultivar identification, linkage mapping and genetic diversity studies. Thus, the combination a highly efficient re-sequencing approach and the SNPlextrade mark high throughput genotyping technology provide a powerful tool for grapevine genetic analysis.
OBJECTIVE: To determine whether luteal phase endometrial transcriptome is altered in obese women during the window of implantation (WOI), considering the presence of infertility, fat distribution and ...association with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: University-affiliated infertility clinic, between May 2007 and March 2009. PATIENT(S): One control group of women with normal weight (n = 4), and four study groups of obese women (n = 6 each one) according to the association with infertility, PCOS, and ovarian stimulation. INTERVENTION(S): The endometrium was biopsied 7 days after LH surge or hCG administration in 28 women. MAIN OUTCOME MEASURE(S): Endometrial gene expression during the WOI. RESULT(S): One hundred and fifty-one genes were dysregulated in obese groups compared with controls. This dysregulation was more pronounced when infertility was associated. The biologic processes of these genes belonged mainly to development and regulation of different biological functions such as transcription and biosynthesis. The molecular functions overrepresented were transcription and peptide receptor activity. The endometrium of obese women with PCOS showed dysregulated genes related to biologic processes such as development, morphogenesis, and the immune system, as well as different molecular functions such as protein binding, binding, growth factor activity, and carboxylic acid transmembrane transporter activity. Some of these genes have been previously related to implantation and unexplained infertility. CONCLUSION(S): Obese women present a different endometrial gene expression than controls during the WOI, which is more pronounced when infertility or polycystic ovary syndrome are associated.
•To calculate the resistance modes of sections (shear, torsion and distortion), in opposition to classical methods.•The orthogonalization of shear warping functions to take into account the shear lag ...effect in a general way.•Describing a new beam element formulating the displacement field and applying energetic methods.•Checking the developed element by comparison with analytical solutions and other known results.
Practical design of bridges and other structures requires the use of quick and simple calculation methods, rather than the use of tridimensional models using shell or solid finite elements. These methods have to be used for a general loading state, taking into account the different structural mechanisms, and generating the results required to apply the verifications of the structural codes and to understand the structural behavior. In this work, a beam-type element is proposed to adress these objetives for the case of thin walled sections. This element has three nodes, with five-degrees of freedom per node, more than the six degrees of a conventional 3D beam, incorporates the effects of shear lag, torsion and distortion homogeneous and non homogeneous in the distribution of normal stress. Various examples were tested to verify the validity of the beam element according different calculation methods.
This study analyses the potential of a learning analytics (LA) based formative assessment to construct personalised teaching sequences in Mathematics for 5th‐grade primary school students. A total of ...127 students from Spanish public schools participated in the study. The quasi‐experimental study was conducted over the course of six sessions, in which both control and experimental groups participated in a teaching sequence based on mathematical problems. In each session, both groups used audience response systems to record their responses to mathematical tasks about fractions. After each session, students from the control group were given generic homework on fractions—the same activities for all the participants—while students from the experimental group were given a personalised set of activities. The provision of personalised homework was based on the students' errors detected from the use of the LA‐based formative assessment. After the intervention, the results indicate a higher student level of understanding of the concept of fractions in the experimental group compared to the control group. Related to motivational dimensions, results indicated that instruction using audience response systems has a positive effect compared to regular mathematics classes.
Practitioner notes
What is already known about this topic
Developing an understanding of fractions is one of the most challenging concepts in elementary mathematics and a solid predictor of future achievements in mathematics.
Learning analytics (LA) has the potential to provide quality, functional data for assessing and supporting learners' difficulties.
Audience response systems (ARS) are one of the most practical ways to collect data for LA in classroom environments.
There is a scarcity of field research implementations on LA mediated by ARS in real contexts of elementary school classrooms.
What this paper adds
Empirical evidence about how LA‐based formative assessments can enable personalised homework to support student understanding of fractions.
Personalised homework based on an LA‐based formative assessment improves the students' comprehension of fractions.
Using ARS for the teaching of fractions has a positive effect in terms of student motivation.
Implications for practice and/or policy
Teachers should be given LA/ARS tools that allow them to quickly provide students with personalised mathematical instruction.
Researchers should continue exploring these potentially beneficial educational implementations in other areas.
Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the ...characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia.
A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared.
Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group.
MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.
To compare the effect of two strategies of antibiotic use (mixing vs. cycling) on the acquisition of resistant microorganisms, infections and other clinical outcomes.
Prospective cohort study in an ...8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam) and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters.
A total of 409 (42%) patients were included in mixing and 560 (58%) in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days). There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5-1.1). Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6-1.2), any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5-1.5), length of stay (median 5 d for both groups) or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7-1.3).
A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality.
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