Deoxynivalenol (DON) remains one of the most concerning mycotoxins produced by the Fusarium genus due to the wide occurrence in highly consumed cereal-based food and its associated toxicological ...effects. Previous studies conducted in Spain and other European countries suggested that some vulnerable groups such as children could be exceeding the tolerable daily intakes. Thus, the aim of this study was to conduct a comprehensive and updated dietary exposure assessment study in Spain, with a specific analysis in the region of Catalonia. Cereal-based food samples collected during 2019 were analysed using liquid chromatography coupled to tandem mass spectrometry for multi-mycotoxin detection including DON and its main metabolites and derivatives. Consumption data were gathered from the nation-wide food surveys ENALIA and ENALIA2 conducted in Spain, and a specific survey conducted in Catalonia. The data were combined using deterministic and semi-parametric probabilistic methods. The results showed that DON was widely present in cereal-based food highly consumed in Spain and the Catalonia region. Exposure to DON among the adult population was globally low; however, among infants aged 3–9 years, it resulted in the median of 192 ng/kg body weight/day and the 95th percentiles of 604 ng/kg body weight/day, that would exceed the most conservative safety threshold for infants. Bread and pasta were the main contributing foodstuffs to the global exposure to DON, even among infants; thus, those foods should be considered a priority for food control or to develop strategies to reduce the exposure. In any case, further toxicological and epidemiological studies are required in order to refine the safety thresholds accounting for the sensitivity of the infant population.
Summary Background We evaluated whether performing contrast-enhanced breast MRI in addition to mammography and/or ultrasound in patients with nonpalpable suspicious breast lesions improves breast ...cancer management. Methods The MONET – study (MR mammography of nonpalpable breast tumours) is a randomised controlled trial in patients with a nonpalpable BIRADS 3–5 lesion. Patients were randomly assigned to receive routine medical care, including mammography, ultrasound and lesion sampling by large core needle biopsy or additional MRI preceding biopsy. Patients with cancer were referred for surgery. Primary end-point was the rate of additional surgical procedures (re-excisions and conversion to mastectomy) in patients with a nonpalpable breast cancer. Findings Four hundred and eighteen patients were randomised, 207 patients were allocated to MRI, and 211 patients to the control group. In the MRI group 74 patients had 83 malignant lesions, compared to 75 patients with 80 malignant lesions in the control group. The primary breast conserving surgery (BCS) rate was similar in both groups; 68% in the MRI group versus 66% in the control group. The number of re-excisions performed because of positive resection margins after primary BCS was increased in the MRI group; 18/53 (34%) patients in the MRI group versus 6/50 (12%) in the control group ( p = 0.008). The number of conversions to mastectomy did not differ significantly between groups. Overall, the rate of an additional surgical intervention (BCS and mastectomy combined) after initial breast conserving surgery was 24/53 (45%) in the MRI group versus 14/50 (28%) in the control group ( p = 0.069). Interpretation Addition of MRI to routine clinical care in patients with nonpalpable breast cancer was paradoxically associated with an increased re-excision rate. Breast MRI should not be used routinely for preoperative work-up of patients with nonpalpable breast cancer.
Superconductive TaN thin films synthesized with reactive direct current (DC) sputtering were grown on silicon substrates at 600°C for 60 min with variations of the N
2
gas flow ratio (R
N2
). The ...microstructure of the thin films was analyzed by transmission electron microscopy (TEM), observing a TaN polycrystalline structure constructed by stacked (200) and (111) planes. The surface morphology for almost all samples was relatively smooth with the exception of the film deposited using the highest R
N2
which showed a considerably higher roughness. Chemical composition was determined by x-ray photoelectron spectroscopy (XPS) analysis. It was revealed that the thin films consist of a tantalum nitride compound with a TaN
x
stoichiometry ranging from 0.43 < x < 1.35. The crystallographic results of the obtained films showed that it evolved from face centered cubic (FCC) TaN structure, preferentially oriented along for low R
N2
, to preferred orientation and later to a crystal phase combination (FCC TaN and tetragonal Ta
3
N
5
) as R
N2
ratios was increased. The electrical resistivity of the TaN thin films presented a clear dependence on the stoichiometry which increased considerably with the nitrogen content. All samples but the one synthesized with the highest R
N2
(which presented an insulation electrical behavior) exhibited the typical stepped superconductor transition, and their superconductive transition temperature (Tc) was reduced as the preferred orientation changed from to the direction. This was correlated with R
N2
and its effect on the crystal growth.
Newcastle disease virus (NDV) is a threat to poultry production worldwide. A better understanding of mechanisms of resistance and susceptibility to this virus will improve measures for NDV prevention ...and control. Males and females from resistant Fayoumi and susceptible Leghorn lines were either challenged with a lentogenic strain of the virus or given a mock infection at 3 weeks of age. The lung transcriptomes generated by RNA-seq were studied using contrasts across the challenged and nonchallenged birds, the two lines, and three time points post-infection, and by using Weighted Gene Co-expression Network Analysis (WGNCA).
Genetic line and sex had a large impact on the lung transcriptome. When contrasting the challenged and nonchallenged birds, few differentially expressed genes (DEG) were identified within each line at 2, 6, and 10 days post infection (dpi), except for the more resistant Fayoumi line at 10 dpi, for which several pathways were activated and inhibited at this time. The interaction of challenge and line at 10 dpi significantly impacted 131 genes (False Discovery Rate (FDR) <0.05), one of which was PPIB. Many DEG were identified between the Fayoumi and Leghorns. The number of DEG between the two lines in the challenged birds decreased over time, but increased over time in the nonchallenged birds. The nonchallenged Fayoumis at 10 dpi showed enrichment of immune type cells when compared to 2 dpi, suggesting important immune related development at this age. These changes between 10 and 2 dpi were not identified in the challenged Fayoumis. The energy allocated to host defense may have interrupted normal lung development. WGCNA identified important modules and driver genes within those modules that were associated with traits of interest, several of which had no known associated function.
The lines' unique response to NDV offers insights into the potential means of their resistance and susceptibility. The lung transcriptome shows a unique response to lentogenic NDV compared to a previous study on the trachea of the same birds. It is important to analyze multiple tissues in order to best understand the chicken's overall response to NDV challenge and improve strategies to combat this devastating disease.
Dehumanization continues to be prevalent today and predicts detrimental intergroup consequences. Thus, it is important to identify novel interventions that reduce dehumanization and explore the ...mechanism(s)—both established (e.g., empathy induction, intergroup contact) and relatively understudied (e.g., humor)—driving the effects. To address this issue, in Study 1 (N = 2,349), we conducted an “intervention tournament” and found that a video (i.e., “Mean Tweets”) of a relatable and diverse group of young Muslims ridiculing Islamophobic comments posted on an online video of a Muslim preschool burning down effectively reduces hostility towards Muslims. Specifically, the Mean Tweets intervention significantly reduced dehumanization of Muslims and, although the effects were weaker, anti‐Muslim policy support. However, a follow‐up study conducted 1 month later revealed that these effects subsided. Next, in a preregistered study (i.e., Study 2) (N = 677), we find that our intervention reliably reduced dehumanization of Muslims, but the reduction of anti‐Muslim policy support was not replicated. While investigating our intervention's effect on anti‐Muslim policy support, we find that our intervention led participants to discount the intervention's intended message, which could have short‐circuited the intervention's effectiveness on policy support. Considering these results, we discuss the potential psychological processes (e.g., humor, message discounting, tone) underlying our dehumanization‐reducing intervention.
Trastuzumab resistance hampers its well-known efficacy to control HER2-positive breast cancer. The involvement of PI3K/Akt pathway in this mechanism is still not definitively confirmed.
We selected ...155 patients treated with trastuzumab after development of metastasis or as adjuvant/neoadjuvant therapy. We performed immunohistochemistry for HER2, ER/PR, epidermal growth factor 1-receptor (EGFR), α-insulin-like growth factor 1-receptor (IGF1R), phosphatase and tensin homologue (PTEN), p110α, pAkt, pBad, pmTOR, pMAPK, MUC1, Ki67, p53 and p27; mutational analysis of PIK3CA and PTEN, and PTEN promoter hypermethylation.
We found 46% ER/PR-positive tumours, overexpression of EGFR (15%), α-IGF1R (25%), p110α (19%), pAkt (28%), pBad (22%), pmTOR (23%), pMAPK (24%), MUC1 (80%), PTEN loss (20%), and PTEN promoter hypermethylation (20%). PIK3CA and PTEN mutations were detected in 17% and 26% tumours, respectively. Patients receiving adjuvant trastuzumab with α-IGF1R or pBad overexpressing tumours presented shorter progression-free survival (PFS) (all P≤0.043). Also, p110α and mTOR overexpression, liver and brain relapses implied poor overall survival (OS) (all P≤0.041). In patients with metastatic disease, decreased PFS correlated with p110α expression (P=0.024), whereas for OS were the presence of vascular invasion and EGFR expression (P≤0.019; Cox analysis).
Our results support that trastuzumab resistance mechanisms are related with deregulation of PTEN/PI3K/Akt/mTOR pathway, and/or EGFR and IGF1R overexpression in a subset of HER2-positive breast carcinomas.
Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of ...HER2-positive breast carcinomas.
We selected 278 HER2-positive breast cancer patients with (n=154) and without (n=124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome.
Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab.
Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients.
A body mass index (BMI) ≥30 kg/m(2) and a waist circumference (WC) ≥80 cm in women (WCF) or ≥90 cm in men (WCM) are reference cardiometabolic risk markers (CMM) for Mexicans adults. However, their ...reliability to predict other CMM (index tests) in young Mexicans has not been studied in depth.
A cross-sectional descriptive study evaluating several anthropometric, physiological and biochemical CMM from 295 young Mexicans was performed. Sensitivity (Se), specificity (Sp) and Youden's index (J) of reference BMI/WC cutoffs toward other CMM (n = 14) were obtained and their most reliable cutoffs were further calculated at Jmax.
Prevalence, incidence and magnitude of most CMM increased along the BMI range (p < 0.01). BMI explained 81 % of WC's variance Se (97 %), Sp (71 %), J (68 %), Jmax (86 %), BMI = 30 kg/m(2) and 4-50 % of other CMM. The five most prevalent (≥71 %) CMM in obese subjects were high WC, low HDL-C, and three insulin-related CMM Fasting insulin, HOMA-IR, and QUICKI. For a BMI = 30 kg/m(2), J ranged from 16 % (HDL-C/LDL-C) to 68 % (WC), being moderately reliable (Jmax = 61-67) to predict high uric acid (UA), metabolic syndrome (MetS) and the hypertriglyceridemic-waist phenotype (HTGW). Corrected WCM/WCF were moderate-highly reliable (Jmax = 66-90) to predict HTGW, MetS, fasting glucose and UA. Most CMM were moderate-highly predicted at 27 ± 3 kg/m(2) (CI 95 %, 25-28), 85 ± 5 cm (CI 95 %, 82-88) and 81 ± 6cm (CI 95 %, 75-87), for BMI, WCM and WCF, respectively.
BMI and WC are good predictors of several CMM in the studied population, although at different cutoffs than current reference values.
•The model correctly reproduces the cyclic behavior of tested RC walls.•The model predicts the response of a RC wall building damaged in the Maule earthquake.•Results are consistent with a limited ...ductility seismic behavior of the RC building.•The shear transferred through the bending of slabs significantly increases the ALR.•The vertical ground motion and the damping ratio alter the sequence of wall damage.
Buildings with Reinforced Concrete (RC) walls are commonly used to resist lateral forces in seismic countries because they provide high lateral stiffness and strength. In recent earthquakes, shear wall buildings have shown good behavior in general; however, a small percentage underwent severe damage localized typically in lower stories. Several numerical models have been developed and proposed to simulate the failure mechanism and behavior of RC walls. From the existing models, only those denoted as micro-models can accurately simulate the stress and strain distributions. The aim of this research is double: (i) to validate a nonlinear finite element wall model and the associated material stress-strain constitutive relationship using the behavior of a real building during the 2010 Chile earthquake; and (ii) to analyze the uncertainty of the response of the building due to changes in model parameters. To validate the response of the wall model, four experimental benchmark RC wall specimens were studied, and model accuracy was evaluated using five parameters: initial stiffness, peak base-shear, ultimate base-shear, maximum displacement, and dissipated energy. A sensitivity analysis was carried out to study the influence of material parameters in the wall response and its damage. The case-study is a 18-story building with 1 basement, which suffered severe damage during the 2010 Chile earthquake, which has been studied by non-linear response-history analysis. Uncertainty in the building response due to three important modeling assumptions was considered: Rayleigh’s damping model parameters; effective elastic bending stiffness of the structural elements; and effect of the vertical ground motion component. Results showed that the proposed model can predict the seismic response of the building with reasonable accuracy by identifying correctly the damage location. This case-study enabled us to assess also the effect of damping in non-ductile structures, the important influence of the slab stiffness in the response, and the effect of the vertical ground motion component in the sequence of damaged walls.
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